cell bio exam 4

Why does it take so long for multicellular organisms to develop?

1500 - origin of multicellular eukaryotes.

needed time to become more complex, have more energy, and more cooperation.

All cells must be able to respond to…

signals

Input

• extracellular signal molecule)

• outside of the cell membrane

• does not go inside the cell

• signal passed inside the target cell

Output

• intracellular signal molecules

• inside the cell

• passes messages inside cell, leading to a response.

• signal stays outside, but message is passed along.

Different responses to signals

• grow

• survive + divide

• differentiate

• die

endocrine signaling

secretes hormones into blood or sap (plants) so signals can act over long distances

paracrine signaling

chemicals illicit a response in neighboring cells. may enter bloodstream, but concentrations too low to act over long distances

autocrine signaling

chemicals illicit a response in same cell that produced it

contact-dependent signaling

requires physical interaction of cells

types of signaling

endocrine

paracrine

autocrine

contact dependent

signals can cause

faster or slower responses

fast signaling responses

• seconds to minutes

• signal to receptor

• trigger intracellular signaling pathway

• changes protein that already exists

• no transcription occurs

slow signaling responses

• minutes to hours

• affects DNA —> RNA —> protein synthesis

• makes new proteins (which is why takes longer)

transcriptional responses

• happen in multiple steps

• slower signal responses

• primary and secondary responses

primary responses

The first genes turned on

secondary responses

products of the primary response activate other genes

receptors are needed for cells to __ signals

hear

small nonpolar molecules

(O2, CO2, N2, steroid hormones)

pass easily

small uncharged polar molecules

(H2O, ethanol, glycerol)

pass somewhat

larger uncharged polar molecules

(glucose, nucleosides, some amino acids)

barely pass

ions

(H+, Na+, K+)

can’t pass

all these signals are trying to pass what?

the artificial lipid bilayer

large, water loving signals

cannot cross cell membrane

small, fat loving signals

slip through membrane into cell

The same signal molecule has

different effects on different target cells

(“can mean different things to different cells)

Ex: Acetylcholine

Different cell surface receptors

• ion channel coupled receptors

• enzyme coupled receptors

• g-protein coupled receptors

Kinase

catalyze addition of phosphates groups to molecules. protein kinases are an important group of kinases that attached phosphates groups to proteins. turn “on” signaling proteins.

Phosphatase

catalyzes hydrolytic removal phosphate groups from a molecule. turn “off” signaling proteins.

some intracellular signaling proteins act as __

molecular switches

Signaling by phosphorylation

a critical mechanism in cellular communication and regulation, representing the largest class of signaling pathways. This process involves the addition of phosphate groups to specific amino acids in proteins, primarily serine (Ser), threonine (Thr), and tyrosine (Tyr). The addition of these phosphate groups, mediated by enzymes known as kinases, can alter the activity, location, or interaction of the target proteins, leading to various cellular responses.

Phosphatases, on the other hand, are enzymes that remove phosphate groups, effectively reversing the action of kinases and providing a regulatory mechanism to ensure that signals are terminated appropriately. The balance between kinase and phosphatase activity is crucial for maintaining cellular homeostasis and proper signaling. This phosphorylation and dephosphorylation cycle is involved in numerous biological processes, including cell division, growth, differentiation, and response to environmental stimuli.

Guanine exchange factors

promote the exchange of GDP

for GTP

GTPase-activating proteins

promote GTP hydrolysis

G-protein-coupled receptors

Forms the largest family of cell-surface receptors—more than 700

in humans, and mice have about 1,000 in their sense of smell

alone.

• Signals can be nearly anything, proteins, small peptides, amino-

acid derivatives, or fatty-acid derivatives

• Respond to hormones, paracrine local mediators, and

neurotransmitters

• All have a similar structure: a single polypeptide chain that spans

the membrane seven times

Signaling by GTP binding

is an essential cellular communication mechanism involving proteins known as GTP-binding proteins, which include both trimeric G-proteins and monomeric GTPases. The functional state of these proteins is determined by whether guanosine triphosphate (GTP) or guanosine diphosphate (GDP) is bound to them. When GTP is bound, the protein is considered 'activated' and capable of initiating downstream signaling pathways. In contrast, when GTP is hydrolyzed to GDP, the protein 'turns off,' ceasing its signaling activity.

GTP binding proteins act as molecular switches, rapidly cycling between active and inactive states through GTP binding and hydrolysis. Their activation can be triggered by various extracellular signals, such as hormones or growth factors, and they are crucial in transducing these signals within the cell to elicit appropriate cellular responses, including gene expression, cell growth, and differentiation. The intrinsic GTPase activity of these proteins is fundamental, as it allows them to hydrolyze GTP and revert to their inactive GDP-bound form. This cycle of activation and inactivation is tightly regulated by various factors, including guanine nucleotide exchange factors (GEFs), which promote the exchange of GDP for GTP, and GTPase-activating proteins (GAPs), which enhance the GTPase activity, facilitating the conversion back to the inactive state.

G-proteins

About 20 different types of mammalian G

proteins. Each is activated by a particular set of

target proteins, which are either enzymes or ion

channels in the plasma membrane.

• When G-proteins interact with ion channels,

they cause an immediate change in the state

and behavior of the cell.

• When G-proteins interact with enzymes, the

results are slower and more complex because

they lead to the production of additional

intracellular signaling molecules. The two most

frequent are adenyl cyclase, which makes cyclic

AMP, and phospholipase C, which makes

inositol triphosphate (promotes accumulation

of cytosolic calcium ions) and diacylglycerol

(activates protein kinase C, a ser/thr kinase)

Enzyme-linked cell-surface receptors

Cytoplasmic domains act as enzymes or forms a complex with an

enzyme

• They were identified because they are the receptors for many

growth factors

• Usually have only one transmembrane region

• The largest class consists of receptors that are tyrosine kinases.

• In many cases, ligand binding causes two receptors to dimerize.

Dimerization then activates the enzymatic activity.

• These interactions can trigger large signaling cascades.

Ras

Virtually all receptor tyrosine kinases activate Ras, a small GTP

binding protein that is anchored in the plasma membrane by a

lipid-linkage

• Monomeric GTPase

• Ras initiates a phosphorylation cascade in which a series of ser/thr

kinases phosphorylate and activate one another in sequence,

carrying the signal from the plasma membrane to the nucleus.

• One pathway activated by it is the mitogen-activated protein-

kinase pathway (MAP-kinase pathway)

Cells must…

integrate all of the signals and produce a response

two types of receptors

• cell surface receptors

• intracellular receptors

cell surface receptors

• for molecules that cannot enter the cell

• signal binds to receptor on membrane

• receptor sends message inside (intracellular signaling)

• cell responds (signal stays outside)

intracellular receptors

• molecules that can enter the cell

• signal crosses membrane

• binds receptor inside cell (often in nucleus)

• directly affects DNA —> gene expression

• causes slow (transcriptional) responses