Chapter 16 and 17 cell bio

Chapter 16: Define signal transduction and list the basic components involved in this process in cells.

Chapter 16: Define signal transduction and list the basic components involved in this process in cells.

the signals that pass between cells the signaling cell produces a particular type of extracellular signal molecule that is detected by the target cell. Target cells possess proteins called receptors that recognize and respond specifically to the signal. signal transduction begins when the receptor on a target cell receives an incoming extracellular signal and then produces intracellular signalling molecules that alter cell behavior.

Distinguish the main types of signal-mediated cell-cell communication and identify the type of extracellular signal molecule involved in each

the signal molecules can be proteins, peptides, amino acids, nucleotides, steroids, fatty acids, derivatives or even dissolved gases.

-the most "public" style cell-cell communication involves broadcasting the signal throughout the whole body by secreting it into the animals bloodstream or plant's sap. the extracellular signal molecules used in this way are called hormones and in animals the cells that produce hormones are called endocrine cells.

-some less public signalling is called paracrine signaling, in this the signal molecules diffuse through the extracellular fluid, remaining in the neighboring of the cell

Outline the main classes of extracellular signal molecules, and describe the types of receptors to which they bind

-Endocrine signalling which secretes the signal into the animals bloodstream. made by endocrine cells in the pancreas

-paracrine signaling which the signal diffuses locally through the extracellular fluid. local mediators on to nearby cells

-neuronal signaling which is signaling that is delivered messages quickly/ specifically to individual target cells through private lines. extracellular signal is called a neurotransmitter

- contact dependent signaling allows adjacent cells that initially similar to become specialized to form different cell types

Explain how the same signal molecule can induce different responses in different target cells

a cell reacts to a signal depends on the set of intracellular signalling molecules each cell-surface receptor produces and how these molecules alter the activity of the effector proteins which have a direct effect on the behavior of the target cells.

Recall how a combination of signals can evoke a response that is different from the sum of the effects that each signal can trigger on its own

this is called "tailoring" of cells response occurs in part because the intracellular relays systems activated by the different cell signals interact. thus the presence of one signal might enable a cell to survive another might drive to differentiate in some specialized way and another might cause it to divide. in the absence of proper signals, most animal cells are programmed to kill themselves

Differentiate the types of cell responses that occur rapidly with those that take minutes or hours to execute

rapid responses are possible because, in each case the signal affects the activity of proteins that are already present inside the target cell, awaiting their marching order. other response take more time. Cell growth and division when triggered by appropriate signal molecules can take many hours to execute. this is because the response to these extracellular signal requires changes in gene expression and production of new proteins

Name the basic components needed for an extracellular signal molecule to change the behavior of a target cell, and identify the site at which the primary step in signal transduction takes place

transmembrane receptors detect a signal on the outside and relay the message, in a new form across the membrane into the interior cell. the receptor protein performs the primary step in signal transduction it recognizes the extracellular signal and generates new intracellular signals in response.

Review the main functions of an intracellular signaling pathway and identify the steps at which each can take place

intracellular signalling process usually works like a molecular relay race in which the message is passed "downstream" from one intracellular signaling molecule to another, each activating or generating the next signal molecule in the pathway, until a metabolic enzyme is kicked into action the cytoskeleton is tweaked into a new configuration, or a gene is switched off or on.

1. relay the signal onward thereby help spread it through the cell

2. amplify the signal received, making it stronger so that a few extracellular signals molecules are enough to evoke a large intracellular response.

3. detect signals from more than one intracellular signalling pathway an integrate them before relaying a signal onward

4. distribute the signal to more than one effector protein creating branches in the information flow diagram and evoking a complex response

5. modulate the response to the signal by regulating the activity of components upstream in the signaling pathway, a process known as feedback

Compare positive and negative feedback and contrast the types of responses produced by each

feedback regulation, can occur anywhere in the signalling pathway and can either boost or weaken the response to the signal.

-Positive: a component that lies downstream in the pathway acts on an earlier component in the pathway to enhance the response to the initial signal

-Negative: a downstream component acts to inhibit an earlier component in the pathway to diminish the response to the initial signal

Summarize how phosphorylation can act as a molecular switch, and identify the types of proteins that add and remove this chemical modification

the switch is thrown in one direction by protein kinase, which covalently attaches to a phosphate group onto the switch protein, and in the opposite direction by a protein phosphatase, which takes the phosphate off again. the activity of any protein that is regulated by phosphorylation depends on the balance between activities of protein kinase and protein phosphatase.

Ex. serine and threonine kinases/ tyrosine kinases

Distinguish the two main types of GTP-binding proteins

1.) trimeric GTP-binding proteins as known as G-proteins that relay messages from G-protein coupled receptors

2.) monomeric GTPases to help relay their signals. these switch proteins are generally aided by two sets of regulatory proteins that help to hydrolyze GTP. Guanine nucleotide exchange factors (GEFs) activate the protein by exchange of GDP for GTP and GTPases-activating proteins (GAPs) turn them off by promoting GTP hydrolysis

Describe how monomeric GTPases toggle between active and inactive form

toggle between an active and inactive state depending on whether they have GTP or GDP bound to them respectively. once activated by GTP binding many of these proteins have intrinsic GTP hydrolyzing (GTPase) activity, and they shut themselves off by hydrolyzing their bound GTP to GDP

Differentiate the three main classes of cell-surface receptors and provide an example of each.

-all are coupled receptors

1) 1) ion-channel: change the permeability of the plasma membrane to select ions thereby altering the membrane potential and if the conditions are right producing an electrical current

2) g-protein: activate membrane-bound trimeric GTP-binding protein, which then activate/inhibit an enzyme or an ion channel in the plasma membrane, initiating an intracellular cascade

3) enzyme: either act as enzymes or associate with enzymes inside the cell. when stimulated the enzymes can activate a wide variety of intracellular signaling pathways

List some foreign substances that alter physiology by interacting with cell-surface receptors.

cell-surface receptors also provides targets for many foreign substances that interfere with our physiology from heroin and nicotine to tranquilizers and chili peppers. these substances either block or overstimulate the receptor's natural activity. Many drugs and poisons act in this way.

Describe the type of signal transduction carried out by ion-channel-coupled receptors.

these receptors are responsible for the rapid transmissions of signals across the synapses in the nervous system. they convert a chemical signal, in the form of a pulse of secreted neurotransmitter molecules delivered to a target cell, directly into an electrical chemical signal, in the form of change in voltage across the target cell's plasma membrane. when the neurotransmitter binds to ion channel-coupled receptors on the surface of a target cell the receptor alters its conformation so as to open a channel in the target cell's membrane, rendering it permeable.

ex. Na+, K+, Ca 2+

Review the structure of G-protein-coupled receptors (GPCRs) and describe the types of extracellular signal molecules that bind to them

each is made of a single polypeptide chain that threads back and forth across the lipid bilayer seven times. but each is specific for a particular set of receptors and for a particular set of target enzymes or channels in the plasma membrane.

Recall the general structure of a G protein and describe how the protein responds when activated by a GPCR.

composed of three subunits (alpha beta and Y) two of which are tethered to the plasma membrane by short lipid tails. in the unstimulated state, the alpha subunit is GDP bound and the g-protein is idle. when an extracellular signal binds to its receptor the altered receptor activates a G-protein by causing the alpha subunit to decrease its affinity for GDP which is exchanged for GTP.

-alpha subunit and the beta(y) can each interact directly with target proteins in the plasma membrane, which in turn may relay the signal to other destinations in the cell.

Summarize the factors that determine the duration of a GPCR-stimulated response

the longer the target proteins remain bound to an alpha subunit or beta(Y) complex the more prolonged the relayed signal will be.

-the amount of time that the alpha subunit and beta(y) complex remain "switched on" hence available to relay signals also determines how long a responses last. the timing is controlled by the alpha subunit

Contrast how cholera toxin and pertussis toxin exert their effects

disrupting the activation and deactivation of G-protein can have dire consequences on a cell/organism. the protein cholera toxin enters the cell that line the intestine and modifies the alpha subunit of g-protein called Gs. this modification prevents Gs from hydrolyzing when its bound to GTP, thus locking the g-protein in an active state. results in diarrhea and dehydration

-pertussis toxin: alters the alpha subunit on the g-protein called Gi because it inhibits adenylyl cyclase. modification disables the g-protein by locking it into inactive GDP bound state results in coughing

Relate the speeds of the responses produced by G proteins activating an ion channel versus activating a membrane-bound enzyme.

when g-protein with ion channels they cause an immediate change in the state and behavior of the cell, the interaction of activated g-proteins with enzymes in contrast has consequences that are less rapid and more complex as they lead to the production of additional intracellular signalling molecules

Name the classes of enzymes that are the most frequent targets of G proteins, and list the second messenger molecules they produce

the two most frequent enzymes for g-proteins are adenylyl cyclase which produces a small molecules called inositol trisphosphate and diacylglycerol. inositol triphosphate, in turn promotes the accumulation of cytosolic Ca 2+---yet another intracellular signaling molecule. adenylyl cyclase and phospholipase C are activated by different types of G-proteins, allowing cells to couple the production of the small molecules to different extracellular signals. secondary messengers which rapidly diffuse way from their source thereby amplifying and spreading the intracellular signal

Outline how cyclic AMP is produced in response to G protein activation, and recall how caffeine can potentiate this response.

most commonly the activated G protein alpha subunit switches on the adenylyl cyclase, causing a dramatic and sudden increase in the synthesis of cyclic AMP from ATP. to help terminate the signal, a second enzyme called cyclic AMP phosphodiesterase, rapidly converts cyclic AMP to ordinary AMP. One way that caffeine acts as a stimulant is by inhibiting this phosphodiesterase in the nervous system blocking cyclic AMP degradation and thereby keeping the concentration of this second messenger high.

Compare a signaling pathway in which cyclic AMP produces a response within seconds to one in which the response takes minutes or hours to develop.

cyclic AMP phosphodiesterase is continuously active inside the cell. because it eliminates cyclic AMP so quickly, the cytosolic concentration of this second messenger can change rapidly in response to extracellular signals rising or falling tenfold in a matter of seconds. Cyclic AMP is water soluble so it can in some cases carry the signal throughout the cell traveling from the site on the membrane where it is synthesized to interact with proteins located in the cytosol in the nucleus or on other organelles.

Recall the location and action of the second messenger molecules produced by activated phospholipase C.

from GPCRs--the pathway that begins with the activation of the membrane-bound enzyme phospholipase C and leads to an increase in the second messenger's diacylglycerol, inositol triphosphate and CA 2+

-once activated phospholipase C propagates the signal by cleaving a lipid molecule that is a component of the plasma membrane. the molecule is an inositol phospholipid that is present in small quantities in the cytosolic leaflet of the membrane lipid bilayer.

List several biological processes triggered by calcium ions.

-when a sperm fertilizes an egg for example, Ca 2+ channels open the resulting in a rise in cytosolic Ca 2+ triggers the egg to start development for muscles cells, a signal from nerve triggers a rise in cytosolic Ca 2+ that initiates muscle contraction.

-in many secretory cell including nerve cells Ca 2+ triggers secretion

Explain how cells keep the concentration of calcium ions in the cytosol low and how they terminate a calcium ion signal

the concentration of free Ca (2+) in the cytosol of an unstimulated cell is extremely compared to the concentration in the extracellular fluid and in the ER. these differences are maintained by membrane-embedded Ca (2+) pumps that actively remove Ca 2+ from the cytosol sending it either into the ER or across the plasma membrane and out of the cell. As a result a steep electrochemical gradient of Ca (2+) exist across both ER membrane and the plasma membrane.

Review how calcium-responsive proteins such as calmodulin propagate a calcium ion signal.

calmodulin which is present in the cytosol of all eukaryotic cells that have been examined, including those plants, fungi, and protozoa. When Ca (2+) binds to calmodulin the protein undergoes a conformational change that enables it to interact with a wide range of target proteins in the cell altering their activity.

-one particularly important class of targets are calmodulin is the Ca (2+)/ calmodulin-dependent protein kinases (CaM-kinases). when these kinases are activated by binding to calmodulin complexed with Ca (2+) they influence other processes in the cell by phosphorylating selected proteins

Outline how the gas nitric oxide (NO) can act as a signaling molecule to trigger the relaxation of smooth muscle cells.

nitric oxide diffuses readily from its site of synthesis and slips into neighboring cells, the distance the gas diffuses is limited by its reaction with oxygen and water in the extracellular environment, which converts NO into nitrates and nitrites within seconds.

Recall why nitric oxide acts as a paracrine signal only on cells near its site of synthesis.

acetylcholine binds to a GPCR on the endothelial cell surface resulting in activation of Gq and the release of Ca (2+) inside the cell. Ca (2+) then stimulates the nitric oxide synthase, which produces NO from the amino acid arginine. This NO diffuses into smooth muscle cells in the adjacent vessel wall, causing the cells to relax. this relaxation allows the vessel to dilate so that blood flows through it more freely. many nerve cells also use NO to signal neighboring cells: NO released by nerve terminals.

Outline how GPCRs in the photoreceptors of the retina transmit an extremely rapid signal in response to stimulation by light.

this exceptional speed is achieved in spite of the necessary to relay the signal over the multiple steps of an intracellular signaling cascade. But photoreceptors also provide a beautiful illustration of the advantage of intracellular signaling cascades. in particular, such cascades allow spectacular amplification of the incoming signal and allow cells to adapt so as to be able to detect signals of widely varying intensity.

Summarize how adaptation in the intracellular signaling cascade of photoreceptors allows the eye to respond to dim or bright light.

adaptation frequently occurs intracellular signaling pathways that respond to extracellular signal molecules, allowing cells to respond to fluctuations in the concentrations of such molecules regardless of whether they are present in small or large amounts. by taking advantage of positive and negative feedback mechanisms, adaptation this allows a cell to respond equally well to the signaling equivalents of shouts and whispers.

Compare the general structures of GPCRs and enzyme-coupled receptors such as receptor-tyrosine kinases (RTKs).

GPCRs enzyme-coupled receptors are transmembrane proteins that display their ligand-binding domains on the outer surface of the plasma membrane. instead of associating with a G-protein however the cytoplasmic domain of the receptor either acts as an enzyme itself or forms a complex with another protein that acts as an enzyme.

RTKs (receptor tyrosine kinases) are activated in response to extracellular signals. then consider how activated RTKs transmit the signal along two major intracellular signal pathways that terminate at various effector proteins in the target cell.

Review how the binding of a signal molecule activates RTKs to trigger the assembly of an intracellular signaling complex

The phosphorylation of tyrosines on the receptor tails triggers the assembly of an intracellular signaling complex on the tails. The newly phosphorylated tyrosines serve as binding sites for a variety of signaling proteins that then pass the message on to yet other proteins. the binding of a signaling molecule with an RTK activates tyrosine kinase in the cytoplasmic tail of the receptor.

Recall how signals transmitted by RTKs can be terminated.

to help terminate the response the tyrosine phosphorylation is reversed by tyrosine phosphatases which remove the phosphates that were added to the tyrosine of both the RTKs and other intracellular signaling proteins in response to the extracellular signal, in some cases activated RTKs are inactivated in a more brutal way. they are dragged into the interior of the cell by endocytosis and then destroyed by digestion in the lysosomes.

List several intracellular signaling proteins activated by RTKs.

RTKs recruit and activate many kinds of intracellular signaling proteins, leading to the formation of large signaling complexes on the cytosolic tail of the RTK. one of the key members of these signaling complexes if RAS a small GTP-binding protein that is bound by a lipid tail to the cytosolic face of the plasma membrane. all RTKs activate Ras including platelet-derived growth factor (PDGF) receptors, which mediate cell proliferation in wound healing and nerve growth factor (NGF) receptors which play an important part in the development of certain vertebrate neurons

Outline how RTKs activate the MAP kinase signaling module.

Ras initiates a phosphorylation cascade in which a series of serine/threonine kinases phosphorylate and activate one another in carries the signal from the plasma membrane to the nucleus, includes a three-kinases module called the MAP-kinase signaling module, in honor of the final enzyme in the chain, the mitogen-activated protein kinase or MAP kinase. MAP kinase is phosphorylated and activated by an enzyme called logically enough MAP kinase kinase. this protein itself switched on by a MAP kinase kinase kinase (which is activated by Ras).

Indicate how Ras can fuel uncontrolled proliferation in cancer.

the mutation inactivates the GTPase activity of Ras, so that the protein cannot shut itself off, promoting uncontrolled cell proliferation and the development of cancer. about 30% of human cancers contain such activating mutations in a Ras gene; of the cancers that do not , many have mutations in genes that encode proteins that function in the same signaling pathway as Ras.

Review how extracellular signals that promote cell growth and survival activate PI-3-kinase signaling pathways.

one crucially important signaling pathway that these RTKs activate to promote cell growth and survival involves the enzymes phosphoinositide 3-kinase(PI 3-Kinase) which phosphorylates inositol phospholipids in the plasma membrane. these phosphorylated lipids serve as docking sites for specific intracellular signaling proteins, which relocate from the cytosol to the plasma membrane, where they can activate one another.

Compare how Akt promotes cell survival via Bad and stimulates cell growth via Tor.

akt promotes cell growth and survival of many cell types often by inactivating the signaling proteins it phosphorylates. Akt phosphorylates and inactivates a cytosolic protein called bad. in its active state, Bad encourages the cell to kill itself by indirectly activating a cell-suicide programed called apoptosis. phosphorylation by Akt thus promotes cell survival by inactivating a protein that otherwise promotes cell death.

Review how different types of receptors can trigger a rise in the cytosolic concentration of calcium ions.

The calcium ions that give rise to a [Ca2+] signal can come from one or two sources: intracellular Ca2+ stores and external Ca2+ entering across the plasma membrane. Typically, both sources are utilized. The most ubiquitous of the intracellular Ca2+ release mechanisms involves the phosphoinositide specific phospholipase C (PI-PLC)-derived second messenger IP3, which acts by binding to a specific receptor on the endoplasmic reticulum or to a specialized component of the endoplasmic reticulum. The functional IP3 receptor/channel appears to be a homotetramer containing four binding sites for IP3

Describe a method to identify proteins that interact in response to stimulation by an extracellular signal.

one involves using a protein as "bait" isolating the receptor that binds to insulin, one could attach insulin a chromatography column. cells that respond to the hormone are broken open with detergents that disrupt their membrane, releasing the transmembrane receptor proteins. protein-protein interactions in a signal pathway can also be identified by co-immunoprecipitation.

Outline how a set of mutant RTKs can be used to determine which tyrosines serve as docking sites for the intracellular signaling proteins that propagate the signal.

to determine which phosphorylated tyrosine on a receptor tyrosine kinase (RTKs) is recognized by a certain intracellular signaling protein, a series of mutant receptors can be constructed, each missing a different from its cytoplasmic domain. in this way, the specific tyrosine required for binding can be determined. similarly one can determine whether this phosphotyrosine docking site is required for the receptor to transmit a signal to the cell.

Review how a technology such as RNA interference or CRISPR can be used to assess the importance of a particular protein in a signaling pathway.

the activity of a specific signaling protein can be inhibited or eliminated. in this case of Ras, for example one could shut down the expression of the Ras gene in cells by RNA interference or CRISPER. such cells do not proliferate in response to extracellular mitogens, indicating the importance of normal Ras signaling in the proliferative response

Explain how mutant proteins can be used to determine the order in which proteins participate in a signaling pathway.

to search in which a signaling pathway is not functioning properly. by examining enough mutant animals, many of the genes that encode the protein involved in a signaling pathway can be identified. to determine whether these proteins lie upstream or downstream of Ras one could create cells that express an inactive mutant to form of each protein and then ask whether these mutant cells can be "rescued" by the addition of a continuously active form of Ras.

Review how the Notch receptor activates target genes in response to activation by Delta, and explain how this pathway controls the specialization of nerve cells in developing Drosophila embryos.

notch is crucially important receptor in all animals, both during development and in adults. among other things, it controls the development of neutral cells in drosophila. in this signaling pathway the receptor itself acts as a transcription regulator. when activated by binding of Delta, a transmembrane signal protein on the surface of a neighboring cell, the notch receptor is cleaved. this cleavage releases the cytosolic tail of the receptor, which is then free to move to the nucleus where it helps to activate the approperiate set of notch responses.

Outline how steroid hormones trigger the transcription of different sets of target genes.

cortisol, estradiol, and testosterone and the thyroid hormones such as thyroxine. all of these hydrophobic molecules pass through the plasma membrane of the target cell and bind to receptor proteins located in either the cytosol or the nucleus. regardless of their initial location, these intracellular receptor proteins are referred to as nuclear receptors because when activated by hormone binding they enter the nucleus, where they regulate transcription.

Contrast the cell signaling systems used by plants and animals.

plants make extensive use of transmembrane cell-surface receptors--especially enzyme-coupled receptors. they spindly weed arabidopsis thaliana, has hundreds of genes encoding receptor serine and threonine kinases. but they are structurally different then the receptors found in animals. the plant receptors are thought to play an important part in a large variety of cell signaling processes including those governing plant growth, development and disease resistant. in contrast to animal cells, plant cells seem not to use RTKs, steroid hormones type nuclear receptors or cyclic AMP they seem to use few GPCRs.

Describe how the ethylene signaling pathway regulates ripening of fruits.

systems in plants mediates the response of cells to ethylene-a gaseous hormone that regulates a diverse array of developmental processes, including seed germination and fruit ripening. ethylene receptors are not evolutionary related to any of the class receptors proteins before. it is the empty receptor that is active in the absence of ethylene the empty receptor activates an associated protein kinase that ultimately shuts off the ethylene-responsive genes in the nucleus.

Explain how multiple signaling pathways can integrate information to produce a coordinated cell response.

integration is made possible by connection and interactions that occur between different signaling pathways. such a cross walk allows the cell to bring together multiple streams of information and react to a rich combinations of signals.

Chapter 17: Contrast the structures of the subunits that form intermediate filaments, actin filaments, and microtubules.

cytoskeleton is built on a framework of three types of protein filaments: intermediate filament, microtubules, and actin filament. Each type of filament has distinct mechanical properties and is formed from a different protein subunit. a family of fibrous proteins forms the intermediate filaments; globular tubulin subunits form microtubules; and globular actin subunits form actin filaments

Describe the location and main function of intermediate filaments.

intermediate filaments main function is to enable cells to withstand the mechanical stress that occurs when cells are stretched. in the smooth muscle cells where they were first discovered, their diameter is about 10 nm is between that of the thinner actin filaments and the thicker myosin filaments, are the toughest and most durable of the cytoskeleton filaments. found in the cytoplasm of most animal cells typically form a network throughout the cytoplasm surrounding the nucleus and extending out to the cell periphery

Recall how the structure of intermediate filaments relates to their strength and durability.

is like a rope in which many long strands are twisted together to provide tensile strength- an ability to withstand tension without breaking. fibrous subunits each containing central elongated rod domain with distinct unstructured domains at either end.

Summarize how intermediate filaments are assembled and describe their polarity.

the rod domain consists of an extended alpha helical region that enables pairs of intermediate filament proteins to form stable dimers wrapping around each other in a coiled-coil configuration. two of these coiled-coil dimers running in opposite directions associate to form a staggered tetramer. these tetramers are soluble subunits of intermediate filaments. because the two dimers point in the opposite directions both ends of the tetramer are the same as the two ends of assembled intermediate filaments. depend on noncovalent bonding; it is the combined strength of the overlapping lateral interactions along the length of the proteins that gives intermediate filaments their great tensil strength.

Review how intermediate filament proteins can differ from one another and how these differences relate to the function of the intermediate filament.

the central rod domains of different intermediate filaments proteins are all similar in size and amino acid sequence so that when they pack together they always form filaments of similar diameter and internal structure. by contrast, the terminal head and tail domains vary greatly in both size and amino acid sequence from one type of intermediate filament protein to another. these unstructured domains are exposed on the surface of the filaments, where they allow it to interact with specific components in the cytoplasm

1) keratin filaments in epithelial cells

2) vimentin and vimentin related filaments in connective tissue cells, muscle cells, and supporting cells of the nervous system

3) neurofilaments in nerve cells

4) nuclear lamins which strengthen the nuclear envelope

Describe three disorders that involve defects in intermediate filaments.

keratin genes mutation can form a rare human disease called epidermolysis bullosa simplex where the skin is highly vulnerable to mechanical injury, and even gentle pressure can rupture its cells, causing the skin to blister.

neurofilaments can form neurodegenerative disease amyotrophic lateral sclerosis. axon degeneration and muscle weakness and muscle weakness seen in patients

Compare the structure of the nuclear lamina with that of cytoplasmic intermediate filaments.

whereas cytoplasmic intermediate filaments form ropelike structures the intermediate filaments lining and strengthening inside surface of inner nuclear membrane are organized as two dimensional meshwork. the intermediate filaments that form this tough nuclear lamina are constructed from a class of intermediate filament proteins called lamins. the nuclear lamina disassembles and re-forms at each cell division when the nuclear envelope breaks down during mitosis and then reforms in the daughter cells.

Review how the nuclear lamina disassembles and re-forms during each cell division

collapse and reassembly of the nuclear lamina is controlled by the phosphorylation and dephosphorylation of the lamins. phosphorylation of lamins by protein kinases weakens the interactions between the lamin tetramers and causes the filaments to fall apart. dephosphorylation by protein phosphatases at the end of mitosis allows the lamins to reassemble

Recall how intermediate filaments are stabilized by cross-linking accessory proteins, and explain how these proteins help to position the nucleus within the cell interior.

intermediate filaments are further stabilized and reinforced by accessory proteins such as plectin that cross link the filaments into the bundles and connect them to microtubules to actin filaments and to adhesive structures in desmosomes. plectin and other proteins also interact with protein complexes that link the cytoplasmic cytoskeleton to structures in the nuclear interior, including chromosomes and nuclear lamina. these bridges which span the cytoskeleton and they are involved in many processes, including the movement and positioning of the nucleus within the cell interior and the overall organization of the cytoskeleton.

Review the general location and functions of microtubules

these long and relatively stiff, hollow tubes of proteins can rapidly disassemble in one location and reassemble one another. in a typical animal cell microtubules grow from a small structure near the center of the cell called the centromere. extending out towards the cell periphery, they create a system of tracks within the cell along with vesicles, organelles and other cell components can be transported. the cytoplasmic microtubules are the part of the cytoskeleton mainly responsible for transporting and positioning membrane-enclosed organelles within the cell for guiding the intracellular transport of various cytosolic macromolecules

List several examples of organizing centers from which microtubules grow

extending out towards the cell periphery, they create a system of tracks within the cell along with vesicles, organelles and other cell components can be transported. the cytoplasmic microtubules are the part of the cytoskeleton mainly responsible for transporting and positioning membrane-enclosed organelles within the cell for guiding the intracellular transport of various cytosolic macromolecules

Describe the structure of microtubules and recall how microtubules are assembled from tubulin dimers

molecules of tubulin each of which is a dimer composed of two very similar globular proteins called alpha-tubulin and beta-tubulin, bound tightly together again by noncovalent interactions. the tubulin dimers stack together again by noncovalent bonding to form the wall of hollow, cylindrical microtubule.

State the polarity of a microtubule and summarize how this polarity affects its assembly and function.

tubelike structure is made of 13 parallel protofilaments, each linear chain of tubulin dimers with alpha and beta tubulin alternating along its length. each protofilament has a structural polarity with alpha tubulin exposed at one end and beta tubulin at the other and this polarity is the same for all the protofilaments in the microfilaments. thus the microtubule as a whole has a structural polarity the end with beta tubulin showing is called plus end and the opposite end which contains exposed alpha tubulin is called minus end

Describe the structure of a centrosome and review how the centrosome nucleates the growth of microtubules

the centromere--which is typically close to the cell nucleus when the cell is not in mitosis--organizes and array of microtubules that radiates outward through the cytoplasm. the centrosome consists of a pair of centrioles surrounded by a matrix of proteins. the centrosome matrix includes hundreds of ring shaped structures formed from a special type of tubulin called y-tubulin and each y-tubulin ring complex serves as the starting point or nucleation site for the growth of one microtubule.

Explain why microtubules require organizing centers such as centrosomes to nucleate their growth.

it is much harder to start a new microtubule from scratch, by first assembling a ring of alpha/beta tubulin dimers, than it is to add such dimers to a preexisting y-tubulin ring complex. although purified alpha/bet-tubulin dimers at a high concentration can polymerize into microtubules spontaneously in vitro, the concentration of free alpha/beta in a living cell is too low to drive the difficult first step of assembling the initial ring of a new microtubule. by providing organizing centers at specific sites and keeping the concentration of free alpha/beta-tubulin dimers low cells can control precisely where microtubules form

Describe dynamic instability and indicate how this behavior relates to microtubule function.

behavior of switching back and forth between polymerization and depolymerization. it allows microtubules to undergo rapid remodeling and is crucial for their function. the microtubule may shrink partially and then to no less suddenly start growing again or it may disappear completely to be replaced by new microtubule that grows from the same y-tubulin ring complex.

Summarize how dynamic instability is controlled by GTP hydrolysis.

the dynamically instability of microtubules stems from the intrinsic capacity of tubulin dimers to hydrolyze GTP. this energetically favorable reaction which generates GDP and inorganic phosphate is similar to the hydrolysis of ATP. each free tubulin dimer contains one GTP molecule tightly bound to a beta-tubulin, which hydrolyzes the GTP to GDP shortly after the dimer is added to a growing microtubule. the GDP produced by this hydrolysis remains tightly bound to the beta-tubulin.

Contrast the actions of colchicine and Taxol and explain why both are used to treat human cancers

colchicine: which binds tightly to free tubulin dimers and prevents their polymerizations into microtubules, the mitotic spindle rapidly disappears the cell stalls in the middle of mitosis unable to partition the chromosomes into two groups. the mitotic spindle is normally maintained by a balanced addition and loss of tubulin subunits; when tubulin addition is blocked by colchicine tubulin loss continues until the spindle disappears

taxol: its binds tightly to microtubules and prevents them from losing subunits. because new subunits can still be added the microtubules can grow but cannot shrink.

Recall how and why cells modify the dynamic instability of their microtubules.

cells are able to modify the dynamic instability of their microtubules for particular purposes. microtubules become more dynamic, switching between growing and shrinking much more frequently than cytoplasmic microtubules normally do. this change enables microtubules to disassemble rapidly and then reassembles into the mitotic spindle. when a cell has differentiated into a specialized cell type, the dynamic instability of its microtubules is often suppressed by proteins that bind to the ends or sides of the microtubules and protect them against disassembly. the stabilized microtubules then serve to maintain the organization of the differentiated cell

Compare the movement of cell components—including organelles, membrane vesicles, and macromolecules—by free diffusion and by microtubule-guided transporting

it is cytoplasm is seen to be continual motion, the mitochondria and the smaller membrane enclosed organelles and vesicles travel in small jerky steps- moving for a short period stopping then moving. This saltatory movement is much more sustained and directional than the continual small, brownian movements caused by random thermal movements. these movements can occur along either microtubules or actin filaments. in both cases the movements are driven by motor proteins, which use the energy derived from repeated cycles of ATP hydrolysis to travel steadily along the microtubules or actin filament in a single direction. because motor proteins also attach to other cell components they can transport this cargo along the filaments

Outline how microtubules participate in cell polarization

most differentiated animal cells are polarized; that is one of the cell is structurally or functionally different from the other. cells specialized for secretion have their golgi apparatus positioned toward the site of secretion. the cells polarity is a reflection of the polarized system of microtubules in its interior, which help to position organelles in their required location within the cell and to guide the streams of vesicular and macromolecular traffic moving between one part of the cell to another.

Compare kinesins and cytoplasmic dyneins in terms of their structure, their movement along the microtubule, and how they interact with cargo.

the motor proteins that move along cytoplasmic microtubules, such as those in the axon of a nerve cell, belong to two families; the kinesins generally move toward the plus end of a microtubule (outward from the cell body), the dyeins move toward the minus end (toward the cell body). kinesins and cytoplasmic dyneins are generally dimers that have two globular ATP-binding heads and a single tail members of second class of dyneins. they both interact with microtubules in a stereospecific manner so that the motor protein will attach to a microtubules in only one direction. the tail of motor protein binds stably to some cell component such vesicle or organelle and there by determines the type of cargo that the motor protein transports.

Compare the roles that kinesins and cytoplasmic dyneins have in positioning the organelles in a eukaryotic cell, and describe the effect that colchicine treatment has on organelle placement

kinesins attach to the outside of the ER membrane pull the ER outward along the microtubule stretching it like a net. cytoplasmic dyneins attach to the golgi membranes pull the golgi apparatus along microtubules in the opposite direction, inward toward the nucleus. but when treated with colchicine a drug that promotes microtubule disassembly both the ER and Golgi apparatus change their location dramatically. the Er which is physically connected to the nuclear envelope collapses around the nucleus and the golgi which is not attached to any other organelle fragments into small pieces small vesicles which then disperse throughout the cytoplasm.

Summarize how fluorescent marker proteins and non-hydrolyzable ATP analogs can be used to study the activity of motor proteins such as kinesin or myosin.

observation of kinesin molecules labeled with a fluorescent marker protein revealed that this motor protein marches along microtubules processively-that is each molecule takes multiple steps along the filaments before falling off. combingine of these observations with assays of ATP hydrolysis, researchers have confirmed that one molecule of ATP is hydrolyzed per step. kinesin can move in a processive manner because it have two heads. this enables it to walk toward the plus end of the microtubules in a "hand over hand fashion"

Compare the functions and movements of cilia and flagella

-cilia are hairlike structures covered in plasma membrane, that extend from the surface of many kinds of eukaryotic cells. each cilium contains a core stable microtubules arranged in a bundle, that grow from a cytoplasmic basal body which serves as an organization center. motile cilia beat in a whiplike fashion either to move fluid over the surface of a cell or to propel single cells through a fluid.

-flagella that propel sperm and many protozoa are usually much longer than cilia are. they are designed to move the entire cell rather than moving fluid across the cell surface. flagella propagate regular waves along their length, propelling the attached cell along.

Describe the arrangement of microtubules inside a cilium or flagellum.

each cilium contains a core stable microtubules arranged in a bundle, that grow from a cytoplasmic basal body which serves as an organization center.

the movement of a cilium or flagellum is produced by bending that takes place as its microtubules slide against each other. the microtubules are associated with numerous accessory proteins which project a regular positions along the length of the microtubule bundle.

Outline how ciliary dynein allows a cilium to bend.

ciliary dynein is attached by its tail to one microtubules in each other doubtlet while its globular heads interact with the adjacent microtubules to generate a sliding force between the two microtubules. because of the multiple links the adjacent microtubules is converted to a bending motion.

List several cell structures formed by actin filaments.

depending on which of these proteins they associate with actin filaments can form stiff and stable structures such as:

microvilli on the epithelial cells lining the intestine

small contractile bundles that contract and act like tiny muscles in most animal cells. they also can form temporary structures such as dynamic protrusions formed at the leading edge of a crawling cell or the contractile ring that pinches the cytoplasm in two when an animal cell divides

Compare actin filaments and microtubules in terms of width, length, polarity, and cross-linking.

each filament is a twisted chain of identical globular actin monomers of all which point in the same direction along the axis of the chain. like a microtubule therefore an actin filament has a structural polarity with a plus end and minus end. actin filaments are thinner, more flexible and usually shorter than microtubules, there are however many more of them so the total length of all actin filaments in a cell is generally many times greater than the total length of all the microtubules. they are generally found in cross-linked bundles and networks which are much stronger than individual filaments

Compare the polymerization of actin filaments to that of microtubules.

like microtubules, actin filaments can grow by the addition of monomers at either end but like their rate of growth is faster at the plus end than at the minus end. a naked actin filament like a microtubule without associated proteins is inherently unstable and it can disassemble from both ends. in living cells free actin monomers carry a tightly bound nucleoside triphosphate in this case ATP.

Explain treadmilling and identify the conditions under which this behavior takes place.

at the minus end in contrast ATP is hydrolyzed faster than a new monomers can be added; because ADP actin destabilizes the structure the filaments loses subunits from its minus end at the same time as it adds them to the plus end. individual monomers this move through the filament from the minus end a behavior called treadmilling. when the rates of addition and loses are equal the filament remains the same size

Compare the actions of cytochalasin and phalloidin and describe their effects on cell behavior.

actin filament function can be perturbed experimentally by certain toxins such as cytochalasin to prevent actin polymerization or others such as phalloidin stabilize actin filaments against depolymerization. addition of these toxins to cells or tissues even in low concentration instantaneously freezes cell movements such as cell locomotion. thus as with microtubules many of the functions of actin filaments depend on the ability of the filament to assemble and disassemble. the rates of which depend on the dynamic equilibrium between the actin filaments, the pool actin monomers and various actin-binding proteins

Outline the functions of common actin-binding proteins, including thymosin, profilin, formins, actin-related proteins (ARPs), and myosin

cells contain small proteins such thymosin and profilin that bind to actin monomers in the cytosol, preventing them from adding to the ends of the actin filaments. by keeping actin monomers in reserve until required these proteins play crucial role in regulating actin polymerization. when actin filaments are needed other actin binding proteins such as forminins and actin related proteins to promote actin polymerization.

-Myosins are a large super-family of motor proteins that move along actin filaments, while hydrolyzing ATP to forms of mechanical energy that can be used for a variety of functions such as muscle movement and contraction

Describe the structure and function of the cell cortex.

highly concentrated in a layer just beneath the plasma membrane called the central cortex. actin filaments are linked by actin binding proteins into a meshwork that supports the plasma membrane and gives it mechanical strength. the rearrangement of actin filaments within the cortex provide much of the molecular basis for changes in both cell shape and cell locomotion

Differentiate between lamellipodia and filopodia.

a crawling fibroblast in culture regularly extends thin, flattened lamellipodia at its leading edge. these extensions contain a dense meshwork of actin filaments oriented so that most of the filaments have their plus end close to the plasma membrane. many cells also extend thin, stiff protrusions called filopodia both at the leading edge and elsewhere on the surface. are both exploratory motile structures that form and retract with great speed, moving at around 1 um per second. these protrusions are thought to be generated by the rapid local growth of actin filaments, which assemble close to the plasma membrane and elongated by the additions of actin monomers at their plus end.

Distinguish the roles played by actin in the protrusion, attachment, and contraction involved in cell movement

the molecular mechanisms of these and other forms of cell crawling entail coordinated changes among many molecules in different regions of the cell; there is no single easily identifiable locomotory organelle such as flagellum, three interrelated processes are known as essential (1) the cell sends out protrusions at its "front" or leading edge. (2) these protrusions adhere to the surface over which the cell is crawling and (3) the rest of the cell drags itself forward by traction on these points of anchorage

Explain how ARPs and formins aid in the assembly and extension of protrusions at the cell's leading edge.

promote the formation of a web of branched actin filaments in a lamellipodia. ARPs form complexes that bind to the sides of existing actin filaments and nucleate the formation of new filaments, which grow out at an angle to produce side branches. with the aid of additional actin binding proteins. this web undergoes continual assembly at the leading edge and disassembly further back, pushing the lamellipodium forward.

Summarize how different members of the Rho family of GTPases alter the organization of actin filaments

these extracellular signals act through a variety of cell-surface receptor proteins, which activate various intracellular pathways. many of these pathways converge on a group of closely related monomeric GTPases that are part of the Rho protein family. monomeric GTPases behave as molecular switches that control intracellular processes by cycling between an active GTP-bound site and an inactive GDP-bound state. different RHO family members alter the organizations of actin filaments in different ways

Compare the structure, binding properties, and general function of myosins I and II.

myosin-1 molecules which are present in all cell types, have a head domain and a tail. the head domain binds to an actin filament and has the ATP hydrolyzing motor activity that enables it to move along the filament in a repetitive cycle of binding, detachment and rebinding. the tail varies among the different types of myosin-1 and determines what type of cargo the myosin will carry.

myosin 2: structurally and mechanistically more complex, muscle cells use of its specialized form to drive muscle contraction. these are proteins who are dimers with two globular ATPases heads at one end and a single coiled-tail at the other. they bind to each other to form a bipolar myosin filament, which smaller contractile muscle contractions

List tissues in which actin and myosin filaments are organized in contractile bundles

myosin filament is like a double headed arrow, with two sets of myosin heads pointing outwards away from the middle. one set binds to actin filaments in one orientation and moves the filaments one way; the other set binds to other actin filaments in the opposite orientation and moves the filaments in the opposite direction. as a result the myosin filaments slides sets of oppositely orientated actin filaments past one another. if actin filament and myosin filaments are organized together in a bundle, the bundle can generate a strong contractile force. clearly seen in muscle contraction, but it also occurs in the much smaller contractile bundles of actin filaments and myosin-2 filaments that assemble transiently in nonmuscle cells, and in the contractile ring that pinches dividing cells into two.

Distinguish the structures of a skeletal muscle fiber and a myofibril.

skeletal muscles are huge, multinucleated individual cells formed by the fusion of many smaller cells. the nuclei of the contributing cells are retained in the muscle fiber and lie just beneath the plasma membrane.

-the bulk of the cytoplasm is made up of myofibrils, the contractile elements of the muscle cell. these cylindrical structures are 1-2 um in diameter and maybe as long as a muscle cell itself. each consists of a chain of identical tiny contractile units or sarcomeres.

Describe the structure of a sarcomere.

each sarcomere is about 2.5 um long and the repeating pattern of sarcomeres gives the vertebrate myofibril a striped appearance. sarcomeres are highly organized assemblies of two types of filaments--actin filaments and myosin filaments composed of a muscle specific form for myosin-2

Outline the sliding-filament mechanism of muscle contraction and relaxation, and describe how ATP binding and hydrolysis drive the conformational changes that underlie this movement.

when a muscle is stimulated to contract, the myosin heads start to walk along the actin filament in repeated cycles of attachment and detachment. during each cycle a myosin head binds and is hydrolyzes one molecule of ATP. this causes a series of conformational changes that move the tip of the head by about 5nm along the actin filament toward the plus end. this movement, repeated with each round of ATP hydrolysis propels the myosin molecule unidirectionally along the actin filament.

Explain how excitation of the muscle cell membrane triggers a rise in the cytosolic concentration of calcium ions.

the neurotransmitter released from the nerve terminal triggers an action potential in the muscle cell plasma membrane. this electrical excitation spreads in a matter of millisecond into a series of membranous tubes, called transverse ( or T) tubules that extend inward from the plasma membrane around each myofibril. the concentration of Ca (2+) in the cytosol rises, Ca (2+) binds to tropomyosin and induces the change in shape.

Summarize how calcium ions trigger muscle contraction and how contraction is subsequently reversed

in response to electrical excitation, which passes along the plasma membrane and to the T tubules, much of this Ca (2+) is released in the cytosol through a specialized set of ion channels that open in the sarcoplasmic reticulum membrane. in rise in cytosolic Ca (2+) concentration activates a molecular switch made of specialized accessory proteins closely associated with the actin filaments.

Explain how calcium ions stimulate contraction in nonmuscle cells or in smooth muscle, and compare this mode of activation with that of skeletal muscle

myosin-2 in nonmuscle cells is also activated by a rise in cytosolic Ca (2+) but the mechanism of activation is different from that of the muscle-specific myosin-2. an increase in Ca (2+) leads to the phosphorylation of nonmuscle myosin-2, which alters the myosin conformation and enables it to interact with actin. a similar activation mechanism operates in a smooth muscle that is present in the walls of a lot of different areas. this mode of myosin activation is relatively slow because time is needed for enzyme molecules to diffuse to the myosin heads and carry out the phosphorylation, and subsequent dephosphorylation. However, this mechanism has the advantage that--unlike the mechanism used by skeletal muscle cells.