~CELL SIGNALING PART

Chapter 45 45.1 Hormones and other signaling molecules bind to target receptors, triggering specific response pathways

• A hormone is a secreted molecule that circulates throughout the body and stimulates specific cells

• Although a given hormone reaches all cells of the body, it only elicits a response

  • In specific target cells, those that have a receptor that binds the hormone specifically

  • Cells lacking receptor for that hormone are unaffected

• Chemical signaling by hormones is the function of the endocrine system, one of the two basic systems for communication and regulation in the animal body

• The nervous system is a network of specialized cells that transmit signals along dedicated pathways

  • These signals in turn regulate the release of hormones

• Communication between animal cells via secreted signals is often classified by the type of secreting cell and the route taken by the signal in reaching its target

  • Endocrine signaling: secreted molecules diffuse into blood stream and trigger responses in target cells anywhere in the body

    • One function is to maintain homeostasis. Hormones regulate properties that include blood pressure and volume, energy metabolism and allocation, and solute concentrations in body fluids. It also mediates responses to environmental stimuli, regulates growth and development, and triggers physical and behavioral changes underlying sexual maturity and reproduction

  • Paracrine signaling: secreted molecules diffuse locally and trigger a response in neighboring cells

  • Autocrine signaling: secreted molecules diffuse locally and trigger a response in the cells that secrete them

    • Local regulators are molecules that act over short distances, reach their target cells solely by diffusion, and act on their target cells within seconds. They play roles in many physiological processes including blood pressure regulation, nervous system function, and reproduction

      • Prostaglandins are a group of local regulators that are produced throughout the body and have diverse functions (ex; in the immune system they promote inflammation and the sensation of pain)

      • Nitric oxide is another local regulator. When the level of oxygen in the blood falls, endothelial cells in blood vessel walls synthesize and release NO

  • Synaptic signaling: neurotransmitters diffuse across synapses and trigger responses in target issues (neurons, muscles, or glands)

  • Neuroendocrine signaling: neurohormones diffuse into the bloodstream and trigger responses in target cells anywhere in the body

  • Pheromones are chemicals that are released into the external environment. They serve a wide range of functions that include defining territories, warning predators, and attracting potential mates

• Hormones fall into three major chemical classes: polypeptides, steriods, and amines.

  • The hormone insulin is a polypeptide that contains two chains in its active form. It is water soluble and hydrophilic

  • Cortisol is a steroid that is derived from cholesterol. It is lipid soluble and hydrophobic

  • Epinephrine and thyroxine are amine hormones, each synthesized from a single amino acid

• Hormones vary in their solubility in aqueous and lipid-rich environments

• Some endocrine cells are found in organs that are part of other organ systems in endocrine glands

  • Endocrine glands secrete hormones directly into the surrounding fluid

  • Exocrine glands have ducts that carry secreted substances onto body surfaces or into body cavities

Chapter 11 11.1 external signals are converted to responses within the cell

• Quorum sensing allows bacterial populations to coordinate the behavior of all cells in a population in activities that require a given density of cells acting at the same time (ex; biofilm, an aggregation of bacterial cells attached to a surface by molecules secreted by the cells, but only after the cells have reached a certain density)

• In yeast, there are two mating types (alpha and beta) and each type secretes a specific factor that binds only to receptors on the other type of cell. When exposed to each other’s mating factors, a pari of cells of opposite type change shape, grow toward each other and fuse (mate). The new alpha/beta cells contains all the genes of both original cells, providing advantages to the cell’s descendants

  • The unique match between mating factor and receptor is key to ensuring mating only between cells of the same species of yeast.

• Binding occurs in three major steps: signal reception, signal transduction, and cellular response — signal transduction pathway

  • These pathways exist in both unicellular and multicellular organisms

• Some animal cells may communicate by direct contact between cell surface molecules. This is especially important in embryonic development, the immune response, and in maintaining adult stem cell populations

  • Cell junctions: both animal and plants have cell junctions that allow molecules, including signaling molecules, to pass readily between adjacent cells without crossing plasma membranes

  • Cell surface molecule: in many animal cells, cell surface molecules on adjacent cells interact with each other, resulting in a signal passing between the cells

• Signal reception: reception is the target cell’s detection of a signaling molecule coming from outside the cell. A chemical signal is detected when the signaling molecule binds to a receptor protein located at the cell’s surface (or inside the cell)

• Signal transduction: the binding of the signal molecule changes the receptor protein in some way, initiation the process of transduction. The transduction stage converts the signal to a form that can bring about a specific cellular response. It sometimes occurs in a single step but more often requires a sequence of changes in a series of different molecules

  • The binding of epinephrine to a receptor protein in a liver cell’s plasma membrane leads to activation of glycogen phosphorylase in the cytosol

• Cellular response: the transduce signal finally triggers a specific cellular response. The response may be almost any imaginable cellular activity. This cell signaling process helps ensure that crucial activities like this occur in the right cells, at the right time, and in proper coordination with the activities of other cells of the organism

11.2 signal reception: a signaling molecule binds to a receptor, causing it to change shape

• The signaling molecule acts as a ligand, the term for a molecule that specifically binds to another molecule. This generally causes a receptor protein to undergo a shape change

• Intracellular receptor proteins are found in either the cytoplasm or nucleus of target cells. To reach such a receptor, a signaling molecule passes through the target cell’s plasma membrane.

  • Most important signaling molecules can do this because they are either hydrophobic enough or small enough to cross the hydrophobic interior of the membrane

• Aldosterone is a hormone that is secreted by cells of the adrenal gland. It travels through the blood and enters cells all over the body. The hormone binds to and activates the receptor protein and with aldosterone attached, the active form of the receptor protein then enters the nucleus and turns on specific genes that control water and sodium flow in kidney cells.

• Special proteins called transcription factors control which genes are turned on

  • When the aldosterone receptor is activated, it acts as a transcription factor that turns on specific genes. This causes the receptor itself to act as the receptor and transducer

11.3 signal transduction: cascades of molecular interactions transmit signals from receptors to relay molecules in the cell

• When receptors for signaling molecules are plasma membrane proteins, the transduction stage of cell signaling is usually a multistep pathway involving many molecules

  • Steps often include activation of proteins by addition or removal of phosphate groups or release of other small molecules or ions that act as signaling molecules.

• An enzyme that transfers phosphate groups from ATP to a protein is generally known as a protein kinase

  • A receptor tyrosine kinase (RTK) is a specific kind of protein kinase that phosphorylates tyrosines on the RTK in a dimer.

• Many signal transduction pathways use relay molecules that are protein kinases, and they often act on other protein kinases in the pathway.

• A phosphorylation cascade is a series of chemical reactions during cell signaling mediated by enzymes, in which each kinase in turn phosphorylates and activates another, ultimately leading to phosphorylation of many proteins

  • The signal is transmitted by a cascade of protein phosphorylations, each causing a shape change in the phosphorylated protein. The shape change alters the function of the protein, most often activating it.

• Together, protein kinases probably regulate the activity of a large proportion of the thousands of protein in a cell.

• Protein phosphatases are enzymes that can rapidly remove phosphate groups from proteins through dephosphorylation

  • Through dephosphorylating and inactivating protein kinases, phosphatases provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present and also make the protein kinases available for reuse, enabling the cell to respond again to extracellular signal

• The phosphorylation-dephosphorylation system acts as a molecular switch in the cell, turning activates on or off, or up or down, as required

• Many signaling pathways also involve small, nonprotein, water soluble molecules or ions called second messengers.

  • Second messengers participate in pathways that are initiated by both G protein coupled receptors and receptor tyrosine kinases (RTKs)

  • The two most common second messengers are cAMP and Ca2+

• Binding epinephrine to the GPCR in the plasma membrane results in a rise in the cytosolic concentration of cAMP, a small molecule produced from ATP

  • An enzyme embedded in the plasma membrane, adenylyl cyclase, converts ATP to cAMP in response to an extracellular signal

  • When epinephrine outside the cell brings to a GPCR, it activates a G protein that in turn actives adenylyl cyclase. Adenylyl cyclase can then catalyze the synthesis of many molecules of cAMP so that the normal cellular concentration can be boosted

  • The immediate effect of an elevation in cAMP level is usually the activation of a protein kinase A. The activated protein kinase A then phosphorylates various other proteins, depending on the cell type

• Further regulation of cell metabolism is provided by other G protein systems that inhibit adenylyl cyclase. In the systems, a different signaling molecule activates a different receptor, which in turn activates an inhibitory G protein that blocks activation of adenylyl cyclase

• In one pathway, the gas nitric oxide is released by a cell and enters a neighboring muscle cell where it causes production of a molecule cGMP which acts as a second messenger that causes relaxation of muscles

• Calcium is more widely used than cAMP as a second messenger

  • Increasing the local cytosolic concentration of Ca2+ causes many responses in animal cells, including muscle contraction, exocytosis of molecules (secretion), and cell division. In plant cells, a wide range of hormonal and environmental stimuli can cause brief increases in cytosolic Ca2+ concentration, triggering various signaling pathways, such as the pathway for greening in response to light

  • Cells use Ca2+ as a second messenger in pathways triggered by both G protein coupled receptors and receptor tyrosine kinases

• In response to a signal relayed by a signal transduction pathway, the cytosolic calcium level may rise. The pathways leading to calcium release involve two other second messengers, inositol triphosphate and diacylglycerol .

  • These two messengers are produced by cleavage of a certain kind of phospholipid in the plasma membrane

11.4 cellular response: cell signaling leads to regulation of transcription or cytoplasmic activities

• Many signaling pathways ultimately regulate protein synthesis, usually by turning specific genes on or off in the nucleus

• Sometimes a signaling pathway may regulate the activity of proteins rather than causing their synthesis by activation gene expression

  • This directly affects proteins that function outside the nucleus (ex; a signal may cause the opening or closing of an ion channel in the plasma membrane or a change in the activity of a metabolic enzyme

• There can be nuclear and cytoplasmic response

• Scaffolding proteins are large relay proteins to which several other relay proteins are simultaneously attached. They increase the efficiency of signal transduction

11.5 apoptosis requires integration of multiple cell signaling pathways

• For a cell to carry out the appropriate response, cellular proteins often must integrate multiple signals

• Cells that are infected, damage, or have reached the end of their functional life span often undergo programmed cell death

  • During this process, cellular agents chop up the DNA and fragment the organelles and other cytoplasmic components. The cell shrinks and becomes lobed, and the cell’s parts are packaged up in vesicles that are engulfed and digested by specialized scavenger cells, leaving no trace.

• Apoptosis protects neighboring cells from damage that they would otherwise suffer if a dying cell merely leaked out all its contents, including its many digestive enzymes

• The signal that triggers all of the complex events that occur during apoptosis can come from either outside or inside the cell

  • Outside the cell, signaling molecules released from other cells can initiate a signal transduction pathway that activates the genes and proteins responsible for carrying out cell death

  • Within a cell whose DNA has been irretrievably damages, a series of protein-protein interactions can pass along a signal that similarly triggers cell death

• There are several different pathways that can carry out apoptosis. The pathway that is uses depends on the type of cell and on the particular signal that initiates apoptosis

  • One major pathway involves certain mitochondrial proteins that are triggered to form molecular pores in the mitochondrial outer membrane, causing it to leak and release other proteins that promote apoptosis

• A built in cell suicide mechanism is essential to development and maintenance in all animals

  Mitosis and the cell cycle : 5.5, 12.1, 12.2 5.5 nucleic acids store, transmit, and help express hereditary information

  • The amino acid sequence of a polypeptide is programmed by a discrete unit of inheritance known as a gene

    • Genes consist of DNA, which belongs to the class of compounds called nucleic acids (- polymers made up of nucleotides)

  • DNA and RNA enable living organisms to reproduce their complex components from one generation to the next

    • DNA provides directions for its own replication and also directs RNA synthesis (and control protein synthesis through RNA (- gene expression))

  • DNA is the genetic material that organisms inherit from their parents

  • Each chromosome contains one long DNA molecule, usually carrying several hundred or more genes

  • When a cell reproduces itself by dividing, its DNA molecules are copied and passed along from one generation of cells to the next

  • The tools that carry out most of the processes in cells consist mostly of proteins

  • A given gene along a DNA molecule can direct synthesis of a tape of mRNA. The mRNA molecule interacts with the cell’s protein-synthesizing machinery to direct production of a polypeptide, which folds into all or part of a protein

    • DNA => RNA => protein

  • Protein synthesis takes place in the ribosomes

  • mRNA conveys genetic instructions for building proteins from the nucleus to the cytoplasm

  • Nucleic acids are macromolecules that exist as polymers called polynucleotides

  • There are two families of nitrogenous bases:

    • Pyrimidines have one six membered ring of carbon and nitrogen atoms. The members of this family are cytosine, thymine, and uracil

    • Purines have a six membered ring fused to a five membered ring. The members of this family are adenine and guanine

  • The sequence of bases along a DNA (or mRNA) polymer is unique for each gene and provides very specific information to the cell

  • The information carried by the gene is encoded in its specific sequence of the four DNA bases

  • The linear order of bases in a gene specifies the amino acid sequence (the primary structure) of a protein

  • tRNA brings amino acids to the ribosome during the synthesis of a polypeptide

  12.1 most cell division results in genetically identical daughter cells

  • The ability of organisms to produce more of their own kind is the one characteristic that best distinguishes living things from nonliving matter

  • The continuity of life is based on the reproduction of cells, or cell division

  • When a prokaryotic cell divides, it is actually reproducing because the process gives rise to a new organism

  • For multicellular eukaryotes, cell division enables each of these new organisms to develop from a single cell - the fertilized egg

  • The reproduction of a cell cannot occur by a mere pinching in half

  • In both prokaryotes and eukaryotes, a crucial function of most cell divisions is the distribution of identical genetic material (DNA) to two daughter cells

    • A dividing cell replicates its DNA, distributes the two copies to opposite ends of the cell, and then splits into daughter cells

  • When a cell is not dividing, and even as it replicates its DNA in preparation for cell division, each chromosome is in the form of a long, thin chromatin fiber.

    • After DNA replication, the chromosomes condense as part of cell division

  • Each duplicated chromosome consists of two sister chromatids, which are joined copies of the original chromosome

  • Later in the cell division process, the two sister chromatids of each duplicated chromosome separate and move into two new nuclei, one forming at each end of the cell. Once the sister chromatids separate, they are no longer called sister chromatids but are considered individual chromosomes

  • Mitosis (- the division of genetic material in the nucleus) is immediately followed by cytokinesis (- the division of the cytoplasm)

  • From a fertilized egg, mitosis and cytokinesis produced the 37 trillion somatic cells that make up our body, and the same processes continue to regenerate new cells to replace the dead and damaged ones

  • Gametes are produced by a variation of cell division called meiosis

  12.2 the mitotic phase alternates with interphase in the cell cycle

  • Mitosis is just one part of the cell cycle, the life of a cell from the time it is first formed during division of a parent cell until its own division into two daughter cells

  • The mitotic phase (- M phase, which includes both mitosis and cytokinesis, and is usually the shortest part of the cell cycle) alternates with a much longer stage called interphase which accounts for about 90% of the cyle

    • Interphase can be divided into three phases: the G1 phase (first gap), the S phase (synthesis), and the G2 phase (second gap)

      • During all three stages a cell grows by producing proteins and cytoplasmic organelles such as mitochondria and endoplasmic reticulum.

      • A cell grows (G1), continues to grow as it copies its chromosomes (S), grows more as it completes preparation for cell division (G2), and divides (M)

  • A particular human cell might undergo one division in 24 hours. Of this time, the M has would occupy less than 1 hour, while the S phase might occupy 10-12 hours, or about half the cycle

    • The rest of the time would be apportioned between the G1 phase and the G2 phases. The G2 phase usually takes 4-6 hours while the G1 phase is the most variable in length.

  • Mitosis is broken down into five stages: prophase, pro metaphase, metaphase, anaphase, and telophase

  • The mitotic spindle begins to form in the cytoplasm during prophase. This structure consists of fibers made of microtubules and associated proteins.

  • While the mitotic spindle assembles, the other microtubules of the cytoskeleton partially disassemble, providing the material used to construct the spindle

  • In animal cells, the assembly of spindle microtubules starts at the centrosome (- sub cellular region containing material that functions throughout the cell cycle to organize the cell’s microtubules)

  • Each of the two sister chromatids of a duplicated chromosome has a kinetochore (- a structure made up of proteins that have assembled on specific sections of DNA at each centromere)

  • At the metaphase, the centromeres of all the duplicated chromosomes are on a plane midway between the spindle’s two poles

  • At the end of anaphase, duplicate groups of chromosomes have arrived at opposite ends of the elongated parent cell

  • Cytokinesis occurs by a process known as cleavage

    • The first sign of cleavage is the appearance of a cleavage furrow (- a shallow groove in the cell surface near the old metaphase plate)

  • In plant cells, there is no cleavage furrow, instead, during telophase, vesicles derived from the Golgi apparatus move along microtubules to the middle of the cell where they produce a cell plate. The cell plate enlarges until its surround membrane fuses with the plasma membrane along the perimeter of the cell, forming to daughter cells

  • During binary fission in bacteria, the chromosome replicates and the daughter chromosomes actively move apart

  • It is likely that mitosis evolved from prokaryotic cell division

    • Certain unicellular eukaryotes exhibit mechanisms of cell division that may be similar to those ancestors of existing eukaryotes