Cell Signaling Exam 4

What is a signal?

A message or stimulus that cells use to communicate with themselves, other cells, or their environment. Usually a chemical molecule called a ligand or agonist.

What is a receptor?

A protein that detects a signal and relays it into the cell. Cell-surface receptors bind extracellular signals and change shape to pass along the message.

What is an intracellular signaling molecule?

A molecule inside the cell that interprets or amplifies a signal.

What is an effector?

A molecule that carries out the cell's response to a signal. Examples: metabolic enzymes, transcription factors, and cytoskeletal proteins.

What is an extracellular signaling molecule?

A molecule outside the cell that starts a signal. It can bind a cell-surface or intracellular receptor depending on its size and chemical properties.

What is contact-dependent signaling?

Communication requiring direct contact between two cells. A membrane-bound signal on one cell binds a membrane-bound receptor on the neighboring cell.

What is paracrine signaling?

A cell releases signaling molecules that act on nearby cells. The molecules travel only a short distance.

What is synaptic signaling?

Neurons send electrical signals along axons and release neurotransmitters at chemical synapses to communicate with target cells.

What is endocrine signaling?

Cells release hormones into the bloodstream so signals can travel throughout the body.

What is signal integration?

A cell receives multiple signals and combines them to decide how to respond. Different combinations of signals can produce different responses.

What is a hyperbolic response?

A response that gradually increases as signal concentration increases, then levels off when receptors become saturated.

What is a sigmoidal response?

An S-shaped response: little response at low signal levels, a steep increase at intermediate levels, then a plateau.

What is an all-or-none response?

A switch-like response where a cell is either OFF or fully ON, with no stable intermediate response. It occurs after a threshold signal level is reached.

What is valency in cell signaling?

The number of signaling molecules that must bind simultaneously to activate a receptor. Higher valency creates a more switch-like response.

What is positive feedback?

The output of a process stimulates that same process, increasing or amplifying the response.

What is negative feedback?

The output of a process inhibits that same process, reducing or stopping the response.

Which signaling molecules must use cell-surface receptors?

Hydrophilic molecules because they are too large and/or polar to cross the cell membrane.

Which signaling molecules can use intracellular receptors?

Small hydrophobic molecules, such as steroid and thyroid hormones, and small gases because they can cross the membrane.

A cancer cell releases molecules that stimulate nearby cancer cells. What signaling type is this?

Paracrine signaling because the molecules act on nearby cells.

A neuron releases acetylcholine that binds receptors on a target cell. What signaling type is this?

Synaptic signaling.

Two neighboring cells communicate through membrane-bound molecules touching. What signaling type is this?

Contact-dependent signaling.

The thyroid releases calcitonin into the bloodstream. What signaling type is this?

Endocrine signaling.

Why can the same signaling molecule cause different responses in different cells?

Different cells have different intracellular signaling molecules and effectors, so the same signal can trigger different responses.

How can signal integration change a cell's response?

Different combinations of signals can cause different decisions, such as cell growth, division, differentiation, or apoptosis.

What are examples of fast versus slow cellular responses?

Fast: changes in neuron signaling, cell movement, and metabolism. Slow: turning on genes to change cell growth and division.

How does valency affect whether a response is hyperbolic or all-or-none?

Low valency allows responses to increase gradually as more receptors bind. High valency requires many molecules to bind before activation, creating a threshold and switch-like response.

What are ion-channel-coupled receptors?

Cell-surface receptors that act as ion channels. A signaling molecule, usually a neurotransmitter, binds and opens the channel.

Where are ion-channel-coupled receptors commonly found?

On postsynaptic cells, across a synapse from a presynaptic neuron.

What are G-protein-coupled receptors (GPCRs)?

Cell-surface receptors that bind signaling molecules and activate G-proteins through conformational changes.

What are G-proteins?

GTP-binding proteins that act as molecular switches and relay signals to cellular effectors.

When are G-proteins ON versus OFF?

ON when bound to GTP; OFF when bound to GDP.

What are enzyme-coupled receptors?

Cell-surface receptors that dimerize after signal binding and activate their own enzymatic activity or another intracellular enzyme.

What is trans-activation of catalytic domains?

When two receptor subunits come together and activate each other's catalytic domains.

How does an ion-channel-coupled receptor become activated?

A ligand, usually a neurotransmitter, binds the receptor and opens its ion channel.

How can an ion-channel-coupled receptor trigger an action potential?

Positive ions enter the postsynaptic neuron, causing depolarization. This opens nearby voltage-gated channels and propagates an electrical signal down the axon.

What is the basic structure of a GPCR?

It has seven transmembrane alpha helices. Extracellular regions bind signals, while intracellular regions interact with G-proteins.

What is the structure of a heterotrimeric G-protein?

It contains three different subunits: alpha, beta, and gamma. The alpha subunit binds GDP or GTP.

How does a GPCR activate a heterotrimeric G-protein?

Ligand binding changes the GPCR's shape. The GPCR acts as a GEF, exchanging GDP for GTP on the alpha subunit. The alpha subunit separates from beta and gamma.

How are GPCRs and enzyme-coupled receptors different?

GPCRs have 7 transmembrane helices and activate G-proteins. Enzyme-coupled receptors have 1 transmembrane helix, dimerize, and activate enzymes.

What does a kinase do?

Adds a phosphate group to a substrate (phosphorylation).

What does a phosphatase do?

Removes a phosphate group from a substrate (dephosphorylation).

What is a GTPase?

An enzyme that hydrolyzes GTP into GDP. G-proteins are active with GTP and inactive with GDP.

What is a guanine nucleotide exchange factor (GEF)?

A protein that causes a G-protein to release GDP and bind GTP, turning it ON.

What is a GTPase-activating protein (GAP)?

A protein that speeds up GTP hydrolysis into GDP, turning a G-protein OFF.

What is a second messenger?

A small intracellular signaling molecule that relays and amplifies a signal inside the cell.

What are examples of second messengers?

cAMP, cGMP, IP3, DAG, and Ca2+.

What is cyclic AMP (cAMP)?

A nucleotide second messenger made from ATP by adenylyl cyclase. It contains one phosphate group linked to the sugar's 3'-OH.

What does adenylyl cyclase do?

Converts ATP into cAMP, producing a second messenger.

What does phosphodiesterase do?

Breaks phosphodiester bonds. It converts cAMP into AMP to help stop the signal.

What is protein kinase A (PKA)?

A protein that becomes activated by binding multiple cAMP molecules and phosphorylates downstream effectors.

What are lipid-derived second messengers?

Signaling molecules produced when phospholipase breaks down PIPs. The two products are DAG and IP3.

What does phospholipase do?

Hydrolyzes PIPs to produce DAG and IP3.

What is DAG?

Diacylglycerol, a lipid-derived second messenger that stays embedded in the cell membrane because of its two fatty acid chains.

What is IP3?

Inositol triphosphate, a hydrophilic second messenger that travels through the cytoplasm to bind target proteins, such as ER Ca2+ channels.

What is a Ca2+ gradient?

A steep electrochemical gradient maintained by cells, with low cytoplasmic Ca2+ compared with the extracellular environment and ER stores.

How does Ca2+ act as a second messenger?

Opening Ca2+ channels allows Ca2+ to enter the cytoplasm, where it binds proteins and continues signaling.

What is calmodulin?

A protein that binds Ca2+ and helps relay signaling messages inside the cell.

What are intracellular signaling complexes?

Groups of signaling molecules assembled near a cell-surface receptor to help relay signals.

What are adaptor proteins?

Proteins that connect other signaling molecules and help recruit them into signaling complexes.

How do GEFs and GAPs regulate G-proteins?

GEFs exchange GDP for GTP to turn G-proteins ON. GAPs speed up GTP hydrolysis to GDP to turn them OFF.

How does one GPCR amplify a signal?

A single ligand-bound GPCR can activate multiple G-proteins, creating a larger response.

What is the main purpose of second messengers?

To amplify and propagate signals inside the cell, coordinate responses, regulate enzymes, and integrate signals.

How does adenylyl cyclase make cAMP?

It uses ATP, removes two phosphate groups, and forms a cyclic phosphodiester bond linking the remaining phosphate to the molecule's 3'-OH.

Which PIP breakdown product opens Ca2+ channels on the ER: DAG or IP3?

IP3 because it is hydrophilic and travels through the cytoplasm to bind ER Ca2+ channels.

Which PIP breakdown product helps activate protein kinase C (PKC): DAG or IP3?

DAG because it remains embedded in the membrane and can recruit PKC.

Why is Ca2+ useful for cell signaling?

Cells maintain a steep Ca2+ gradient. Opening Ca2+ channels allows Ca2+ to enter and bind targets like calmodulin and PKC.

Why assemble intracellular signaling complexes near receptors or membranes?

It brings signaling molecules close together, making it easier and faster for them to interact and relay the signal.What are olfactory receptors? GPCRs on olfactory neurons that bind odorants (small molecules responsible for smell).

What are cAMP-gated cation channels?

Channels that open when cAMP binds, allowing positively charged ions to enter the cell.

Where are cAMP-gated cation channels found?

On olfactory neurons, where cAMP opens them to allow cations into the cell.

What are arrestins?

Proteins that bind phosphorylated, desensitized GPCRs. They block G-protein interaction and can trigger clathrin-mediated endocytosis.

What is olfactory receptor kinase (ORK)?

A kinase that phosphorylates olfactory receptors during persistent odor exposure, helping desensitize the receptor.

What is GPCR desensitization?

A decrease in receptor responsiveness during continuous or repeated signal exposure, preventing overstimulation.

What are rod photoreceptors?

Light-detecting neurons in the retina responsible for black-and-white vision in dim light.

What is rhodopsin?

A GPCR in rod cells that is activated by light and activates a G-protein signaling pathway.

What is cGMP?

Cyclic guanosine monophosphate, a second messenger similar to cAMP but containing guanine instead of adenine.

What does cGMP do in rod photoreceptors?

Keeps cGMP-gated ion channels open in darkness. When cGMP is broken down, the channels close and the cell hyperpolarizes.

What are receptor tyrosine kinases (RTKs)?

Enzyme-coupled receptors with one transmembrane domain. They dimerize after signal binding and phosphorylate tyrosines on each other.

What is autophosphorylation?

When a protein phosphorylates itself. In RTKs, each receptor subunit phosphorylates the other subunit.

What is Ras?

A monomeric G-protein that acts as a molecular switch. It is active when bound to GTP and inactive when bound to GDP.

What are Ras GEFs?

Proteins that turn Ras ON by exchanging GDP for GTP.

What are Ras GAPs?

Proteins that turn Ras OFF by speeding up GTP hydrolysis into GDP.

How does cAMP trigger an action potential in olfactory neurons?

cAMP opens cation channels, allowing Na+ and Ca2+ to enter. This depolarizes the membrane, opens voltage-gated channels, and starts an action potential.

How does prolonged odor exposure desensitize GPCRs?

ORK phosphorylates the GPCR. Arrestin binds the phosphorylated receptor, blocks G-protein interaction, and can cause receptor removal through clathrin-mediated endocytosis.

What enzyme does rhodopsin activate to reduce cGMP?

Phosphodiesterase, which breaks down cGMP into GMP.

What enzyme produces cGMP?

Guanylyl cyclase, which uses GTP to produce cGMP.

Why does light cause rod photoreceptors to hyperpolarize?

Light activates rhodopsin, which activates a G-protein and phosphodiesterase. Phosphodiesterase lowers cGMP, closing cGMP-gated channels and causing hyperpolarization. The rods then release fewer neurotransmitters.

Why must two RTKs come together to activate?

Signal binding brings two receptor subunits together, allowing their intracellular kinase domains to phosphorylate each other.

What happens after RTKs autophosphorylate?

The phosphorylated tyrosines become binding sites that recruit intracellular signaling proteins.

How is Ras similar to heterotrimeric G-proteins?

Both act as molecular switches: GTP-bound is ON and GDP-bound is OFF. GEFs turn them ON and GAPs turn them OFF.

How is Ras different from heterotrimeric G-proteins?

Ras is monomeric, meaning it consists of one polypeptide chain. Heterotrimeric G-proteins contain three subunits: alpha, beta, and gamma.