Bio Chapter 16

4 main styles of cellular communication are?

1. Endocrine 2. Paracrine 3. Synaptic 4. Contact- dependent

What are the 3 main classes of cell surface receptors?

1. Ion- channel receptors- change permeability of membrane to selected ions 2. G- Protein- coupled receptors- activate membrane-bound, trimeric GTP-binding proteins (G proteins) 3. Enzyme- coupled receptors- act as, or asoociate with enzymes inside the cell

What crucial functions do intracellular signaling pathways perform?

1. Relay the signal onward 2. Amplify the signal recieved making it strong 3. detect signals from multiple intracellular pathways and integrate them before relaying forward 4. Distribute the signal to more than 1 effector protein creating branches and creating complex responses

What 2 categories do extracellular molecules fall into?

1. Those that bind to membrane bound receptors on the extracellular surface- polar (hydrophilic, charged) molecules, and large signal molecules 2. Those that bind to intracellular receptros- Nonpolar (hydrophobic, uncharged) molecules, and small signal molecules that often regulate gene expression (ex. steroids and thyroid hormones)

Receipt of extracellular signals can cause changes in cellular physiology. These signals cause changes by altering the cell's cytoplasmic machinery. Some changes occur on a very fast time scale (i.e., in less than a second) whereas other changes occur long after the receipt of a signal (i.e., hours). A. Name an intracellular molecular change that could result in a quick change in cell physiology. B. Name an intracellular molecular change that could lead to a slow change in cellular physiology. C. Explain why the response you named in A results in a quick change while the response you named in B results in a slow change.

A Any answer that involves modification of existing cellular components is correct. For example, protein phosphorylation, protein dephosphorylation, protein ubiquitination, lipid phosphorylation, and lipid cleavage are all examples of correct answers. B. Alterations in gene expression. C. Modification of an existing cellular component can happen quickly, as it involves components (both the modifying protein as well as the substance being modified) that already exist in the cell. Changes in cellular physiology due to changes in gene expression can take much longer, as the gene will need to be transcribed, the mRNA translated, and proteins accumulated to high enough levels to instigate change.

In order to respond to a signal molecule, a cell must have...

A receptor specific for the signal molecule

The rod photoreceptors in the eye are extremely sensitive to light. The cells sense light through a signal transduction cascade involving light activation of a GPCR that activates a G protein that activates cyclic GMP phosphodiesterase. How would you expect the addition of the following drugs to affect the light-sensing ability of the rod cells? Explain your answers. A. a drug that inhibits cyclic GMP phosphodiesterase B. a drug that is a nonhydrolyzable analog of GTP

A. A drug that inhibits cyclic GMP phosphodiesterase would decrease any light response in the rod cell. Normally, cyclic GMP is continuously being produced in the eye. The perception of light by a rod cell normally leads to the activation of cyclic GMP phosphodiesterase, which then hydrolyzes cyclic GMP molecules. This causes Na + channels to close, which changes the membrane potential and alters the signal sent to the brain. If cyclic GMP phosphodiesterase were blocked, levels of cyclic GMP would remain high and there would be no cellular response to light. B. A drug that is a nonhydrolyzable analog of GTP would lead to a prolonged response to light. This is because a nonhydrolyzable analog of GTP would prevent the G protein from turning itself off by hydrolyzing its bound GTP to GDP. Continued activation of the G protein would keep cyclic GMP phosphodiesterase levels higher than normal, leading to a prolonged period of lowered levels of cyclic GMP. This in turn would cause Na + channels to be closed for longer than normal, leading to a prolonged change in the membrane potential and an extended light response.

The rod photoreceptors in the eye are extremely sensitive to light. Rod cells sense light through a signal transduction cascade involving light-activation of a G-protein coupled receptor that activates a G-protein, which activates cyclic GMP phosphodiesterase. Describe how you would expect the addition of the following drugs to affect the light- sensing ability of the rod cells. Explain your answers. A. A drug that is an inhibitor of cyclic GMP phosphodiesterase? B. A drug that is a nonhydrolyzable analog of GTP?

A. A drug that inhibits cyclic GMP phosphodiesterase would decrease any visual responses. Normally, cyclic GMP is continually being produced in the eye. The perception of light by a rod cell normally leads to activation of cyclic GMP phosphodiesterase, which then hydrolyzes cyclic GMP molecules; this causes Na+ channels to close, which changes the membrane potential and alters the signal sent to the brain. If cyclic GMP phosphodiesterase is blocked, levels of cyclic GMP would remain high and there would be no cellular response to light. B. A drug that is a nonhydrolyzable analog of GTP would lead to an extended visual response. This is because a nonhydrolyzable analog of GTP would cause prolonged activation of the G protein in response to light. Continued activation of the G protein would keep cyclic GMP phosphodiesterase levels higher than normal, leading to a prolonged period of lowered levels of cyclic GMP; this in turn would cause Na+ channels to be closed longer than normal, leading to a prolonged change in the membrane potential and an extended visual response.

Receipt of extracellular signals can change cell behavior quickly (for example, in seconds or less) or much more slowly (for example, in hours). A. What kind of molecular changes could cause quick changes in cell behavior? B. What kind of molecular changes could cause slow changes in cell behavior? C. Explain why the response you named in A results in a quick change, whereas the response you named in B results in a slow change.

A. Any answer that involves the modification of existing cell components is correct. Protein phosphorylation, protein dephosphorylation, protein ubiquitylation, lipid phosphorylation, and lipid cleavage are all examples of correct answers. B. Responses that involve alterations in gene expression occur slowly. C. Modification of existing cell components can happen quickly, whereas responses that depend on changes in gene expression take much longer, because the genes will need to be transcribed, the mRNAs will need to be translated, and the proteins need to accumulate to high-enough levels to instigate change.

A calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and memory. This kinase is able to phosphorylate itself such that its kinase activity is now independent of the intracellular concentration of Ca 2+ . Thus, the kinase stays active after Ca 2+ levels have dropped. Mice completely lacking this CaM-kinase have severe spatial learning defects but are otherwise normal. A. Each of the following mutations also leads to similar learning defects. For each case explain why. (1) a mutation that prevents the kinase from binding ATP (2) a mutation that deletes the calmodulin-binding part of the kinase (3) a mutation that destroys the site of autophosphorylation B. What would be the effect on the activity of CaM-kinase if there were a mutation that reduced its interaction with the protein phosphatase responsible for inactivating the kinase?

A. Because a complete lack of the CaM-kinase causes a learning defect, we can assume that mutations leading to inactivation of the kinase would also have a similar effect. (1) Protein kinases have a binding site for ATP, which is the source of the phosphate used for phosphorylating their target proteins; if the kinase cannot bind ATP, it will be inactive. (2) Because binding to calmodulin in the presence of Ca 2+ activates CaM-kinases, deletion of the calmodulin-binding portion would inactivate the kinase. (3) A mutation that destroys the site of autophosphorylation will also impair the normal function of the kinase, because the kinase will become inactive as soon as Ca 2+ levels decrease. Page 31 of 31 B. The kinase would stay active for longer after a transient increase in intracellular Ca 2+ concentration.

Acetylcholine acts at a GPCR on heart muscle to make the heart beat more slowly. It does so by ultimately opening K + channels in the plasma membrane (as diagrammed in Figure Q16-32), which decreases the cell's excitability by making it harder to depolarize the plasma membrane. Indicate whether each of the following conditions would increase or decrease the effect of acetylcholine. A. addition of a drug that stimulates the GTPase activity of the Gα subunit B. mutations in the K + channel that keep it closed all the time C. modification of the Gα subunit by cholera toxin D. a mutation that decreases the affinity of the βγ complex of the G protein for the K + channel E. a mutation in the acetylcholine receptor that prevents its localization on the cell surface F. adding acetylcholinesterase to the external environment of the cell

A. Decrease. An increase in the GTPase activity of the Gα subunit will decrease the length of time that the G protein is active. B. Decrease. If the K + channel remains closed, acetylcholine will not slow the heart. C. Increase. Cholera toxin inhibits the GTPase activity of the Gα subunit, keeping the subunit in an active state for a longer time. D. Decrease. The activated βγ complex binds to and activates the K + channel; decreasing their affinity for each other will decrease the time that the K + channel is open, effectively decreasing the effect of acetylcholine. E. Decrease. If there is no receptor on the cell surface, cells will be unable to respond to acetylcholine. F. Decrease. Acetylcholinesterase degrades acetylcholine and thus will decrease the effect of acetylcholine.

Indicate by writing "yes" or "no" whether amplification of a signal could occur at the particular steps described below. Explain your answers. A. An extracellular signal molecule binds and activates a cell surface receptor. B. The activated G-protein-linked receptors cause Gα to separate from Gβ and Gγ. C. Adenylyl cyclase produces cyclic AMP. D. cAMP activates protein kinase A. E. Protein kinase A phosphorylates target proteins.

A. No. Each signal molecule activates only one receptor. B. No. Each G-protein-linked receptor only activates one heterotrimeric G protein. C. Yes. Each activated adenylyl cyclase molecule can generate many molecules of cAMP. D. No. In unstimulated cells, protein kinase A is held inactive in a protein complex. cAMP binding to the complex induces a conformational change, releasing the active protein kinase A. Therefore, 1 cAMP cannot activate more than 1 molecule of active protein kinase A. E. Yes. Each activated protein kinase A molecule can phosphorylate many molecules of target proteins.

Indicate by writing "yes" or "no" whether amplification of a signal could occur at the particular steps described below. Explain your answers. A. An extracellular signaling molecule binds and activates a GPCR. B. The activated GPCRs cause Gα to separate from Gβ and Gγ. C. Adenylyl cyclase produces cyclic AMP. D. cAMP activates protein kinase A. E. Protein kinase A phosphorylates target proteins.

A. No. Each signaling molecule activates only one receptor molecule. B. Yes. Each activated GPCR activates many G-protein molecules. C. Yes. Each activated adenylyl cyclase molecule can generate many molecules of cAMP. D. No. In unstimulated cells, protein kinase A is held inactive in a protein complex. Binding of cAMP to the complex induces a conformational change, releasing the active protein kinase A. Therefore, one cAMP cannot activate more than one molecule of protein kinase A. E. Yes. Each activated protein kinase A molecule can phosphorylate many molecules of each type of target protein.

A calmodulin-regulated kinase (CaM kinase) is involved in learning and memory. This kinase is able to phosphorylate itself, and the kinase activity of the phosphorylated form is independent of the intracellular concentration of Ca2+. Thus the kinase stays active after Ca2+ levels have dropped. Mice completely lacking this kinase have severe learning defects but are otherwise normal. A. Each of the following mutations also leads to defective memory. For each case explain the reason why. (1) A mutation that prevents the kinase from binding to ATP. (2) A deletion of the calmodulin-binding part of the kinase. (3) A mutation that destroys the site of autophosphorylation. B. What would be the effect on the kinase activity of CaM kinase if there were a mutation that reduced the strength of binding of the kinase to the phosphatase responsible for inactivating the kinase?

A. Since a complete lack of the CaM kinase causes a loss of memory, we can assume that mutations that lead to inactivation of the kinase would also have a deleterious effect on memory. (1) Protein kinases have a binding site for ATP, which is the source of the phosphate used for phosphorylation; if the kinase cannot bind ATP it will be inactive. (2) Since CaM kinases are activated by binding to calmodulin in the presence of Ca2+, deletion of the calmodulin-binding portion would inactivate the kinase. (3) A mutation that destroys the site of autophosphorylation will also impair the normal function of the kinase, since the kinase will become inactive as soon as Ca2+ levels drop. B. Mutations that make the kinase less likely to bind the phosphatase will increase the time that the kinase remains active following a transient increase in Ca2+ levels.

Circle the phrase in each pair that is likely to occur more rapidly in response to an extracellular signal. A. changes in cell secretion / increased cell division B. changes in protein phosphorylation / changes in proteins being synthesized C. changes in mRNA levels / changes in membrane potential

A. changes in cell secretion B. changes in protein phosphorylation C. changes in membrane potential

When adrenaline binds to adrenergic receptors on the surface of a muscle cell, it activates a G protein, initiating an intracellular signaling pathway in which the activated α subunit activates adenylyl cyclase, thereby increasing cAMP levels in the cell. The cAMP molecules then activate a cAMP-dependent kinase (PKA) that, in turn, activates enzymes that result in the breakdown of muscle glycogen, thus lowering glycogen levels. You obtain muscle cells that are defective in various components of the signaling pathway. Referring to Figure Q16-36, indicate how glycogen levels would be affected in the presence of adrenaline in the following cells. Would they be higher or lower than in normal cells treated with adrenaline? A. cells that lack adenylyl cyclase B. cells that lack the GPCR C. cells that lack cAMP phosphodiesterase D. cells that have an α subunit that cannot hydrolyze GTP but can interact properly with the β and γ subunits

A. higher B. higher C. lower D. lower

When adrenaline binds to adrenergic receptors on the surface of a muscle cell, it activates a G-protein, initiating a signaling pathway where the activated Gα subunit activates adenylyl cyclase, increasing cAMP levels in the cell; the cAMP molecules then activate a cAMP-dependent kinase that, in turn, activates enzymes that result in the breakdown of muscle glycogen, thus lowering glycogen levels. You obtain muscle cells that are defective in various components of the G-protein signaling pathway. Indicate how glycogen levels would be affected in the presence of adrenaline in the following cells. Would they be higher, lower, or the same as normal cells that are treated with adrenaline? A. In cells that lack adenylyl cyclase? B. In cells that lack the receptor? C. In cells that lack cAMP phosphodiesterase? D. In cells that have a Gα subunit that cannot hydrolyze GTP but can interact properly with Gβ and Gγ.

A. higher B. higher C. lower D. lower

What are ion channel coupled receptors?

Aka transmitter-gated ion channels, very important in nerve cells, and targets of nerve cells

When the neurotransmitter acetylcholine is applied to skeletal muscle cells, it binds the acetylcholine receptor and causes the muscle cells to contract. Succinylcholine, which has been demonstrated to bind the acetylcholine receptor on skeletal muscle cells, is a muscle relaxant. Succinylcholine is a chemical analog of acetylcholine and is sometimes used by surgeons as a muscle relaxant. Propose a model for why succinylcholine causes muscle relaxation instead of contraction, as acetylcholine does.

Although succinylcholine can bind the acetylcholine receptor, this association does not cause the acetylcholine receptor to alter its conformation and stimulate the intracellular signaling necessary for muscle contraction (which involves, in this case, the opening of ion channels). Succinylcholine prevents normal muscle contraction by competing with acetylcholine for binding to the acetylcholine receptor, thus blocking its action.

When the neurotransmitter acetylcholine is applied to skeletal muscle cells, it binds the acetylcholine receptor and causes the muscle cells to contract. Succinylcholine, which is a chemical analog of acetylcholine, binds to the acetylcholine receptor on skeletal muscle cells but causes the muscle cells to relax; it is therefore often used by surgeons as a muscle relaxant. Propose a model for why succinylcholine causes muscle relaxation. What might be the mechanism to explain the different activities of acetylcholine and succinylcholine on the acetylcholine receptor?

Although succinylcholine can bind to the acetylcholine receptor, it does not activate the receptor and therefore does not cause the muscle cell to contract. Instead, succinylcholine blocks the ability of acetylcholine to bind to the receptor and thereby prevents acetylcholine from stimulating muscle contraction.

For each of the following sentences, select the best word or phrase from the list below to fill in the blanks. Not all words or phrases will be used; each word or phrase should be used only once. An extracellular signal molecule can act to change a cell's behavior by acting through cell-surface __________________ that control intracellular signaling proteins. These intracellular signaling proteins ultimately change the activity of __________________ proteins that bring about cell responses. Intracellular signaling proteins can __________________ the signal received to evoke a strong response from just a few extracellular signal molecules. A cell that receives more than one extracellular signal at the same time can __________________ this information using intracellular signaling proteins. __________________ proteins can act as molecular switches, letting a cell know that a signal has been received. Enzymes that phosphorylate proteins, termed ___________, can also serve as molecular switches; the actions of these enzymes are countered by the activity of __________________. acetylase decouple GTP-binding AMP-binding decrease neurotransmitter amplify effector protein kinases autocrine esterases protein phosphatases cleavage integrate receptorsAn extracellular signal molecule can act to change a cell's behavior by acting through cell-surface receptors that control intracellular signaling proteins. These intracellular signaling proteins ultimately change the activity of effector proteins that bring about cell responses. Intracellular signaling proteins can amplify the signal received to evoke a strong response from just a few extracellular signal molecules. A cell that receives more than one extracellular signal at the same time can integrate this information using intracellular signaling proteins. GTP-binding proteins can act as molecular switches, letting a cell know that a signal has been received. Enzymes that phosphorylate proteins, termed protein kinases, can also serve as molecular switches; the actions of these enzymes are countered by the activity of protein phosphatases. convolute GMP-binding sterols

An extracellular signal molecule can act to change a cell's behavior by acting through cell-surface receptors that control intracellular signaling proteins. These intracellular signaling proteins ultimately change the activity of effector proteins that bring about cell responses. Intracellular signaling proteins can amplify the signal received to evoke a strong response from just a few extracellular signal molecules. A cell that receives more than one extracellular signal at the same time can integrate this information using intracellular signaling proteins. GTP-binding proteins can act as molecular switches, letting a cell know that a signal has been received. Enzymes that phosphorylate proteins, termed protein kinases, can also serve as molecular switches; the actions of these enzymes are countered by the activity of protein phosphatases.

What is chlorea and what causes it?

Bacteria that enter the intestinal cell and produce cholera toxin which modifys the alpha subunit to Gs. This stimulates adenylyl cyclase, however since bound GTP cannot be hydrolyzed, it stays locked in an active state causing prolonged and excessive outflow of Cl- and water into the gut, resulting in diarrhea and dehydration. Whopping cough is also caused this way (Pertussis)

Can signaling via a steroid hormone receptor lead to amplification of the original signal? If so, how?

Because the interactions of the signal molecule with its receptor and of the activated receptor with its gene are both one-to-one, there is no amplification in this part of the signaling pathway. The signal can, however, be amplified when the target genes are transcribed, because each activated gene produces multiple copies of mRNA, each of which is used to make multiple copies of the protein that the gene encodes.

Why do some signals have rapid responses?

Because the proteins that govern these responses are already present

How is the signal from a receptor conveyed?

By a set of intracellular signaling molecules that often alter the activity of effector proteins and are cell type specific

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once. Ca 2+ can trigger biological effects in cells because an unstimulated cell has an extremely __________________ concentration of free Ca 2+ in the cytosol, compared with its concentration in the __________________ space and in the __________________, creating a steep electrochemical gradient. When Ca 2+ enters the cytosol, it interacts with Ca 2+ -responsive proteins such as __________________, which also binds diacylglycerol, and __________________, which activates CaM-kinases. Page 15 of 31 adenylyl cyclase endoplasmic reticulum nuclear average extracellular peroxisome Ca 2+ high phospholipase C calmodulin intracellular protein kinase A colorful low protein kinase C

Ca 2+ can trigger biological effects in cells because an unstimulated cell has an extremely low concentration of free Ca 2+ in the cytosol, compared with its concentration in the extracellular space and in the endoplasmic reticulum, creating a steep electrochemical gradient. When Ca 2+ enters the cytosol, it interacts with Ca 2+ -responsive proteins such as protein kinase C, which also binds diacylglycerol, and calmodulin, which activates CaM-kinases.

Intracellular steroid hormone receptors have binding sites for a signal molecule and a DNA sequence. Give one reason to explain how different cells that have identical intracellular steroid hormone receptors can activate different genes when the receptors bind the same signal molecule.

Cells can respond differently to activated intracellular steroid hormone receptors for several reasons. 1. The cells may differ in the gene regulatory proteins they express for modulating the activity of the activated receptor. 2. Different cells could have their DNA modified in different ways, either through differences in chromatin configuration or differences in the methylation-state of the DNA, which may affect the interaction of the activated receptor with its DNA.

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once. Cells can signal to each other in various ways. A signal that must be relayed to the entire body is most efficiently sent by __________________ cells, which produce hormones that are carried throughout the body through the bloodstream. On the other hand, __________________ methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events. During __________________ signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells. Finally, __________________ signaling involves the conversion of electrical impulses into a chemical signal. Cells receive signals through a __________________, which can be an integral membrane protein or can reside inside the cell. amplification G-protein phosphorylation contact-dependent K+ channel receptor endocrine neuronal target epithelial paracrine

Cells can signal to each other in various ways. A signal that must be relayed to the entire body is most efficiently sent by endocrine cells, which produce hormones that are carried throughout the body through the bloodstream. On the other hand, contact-dependent methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events. During paracrine signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells. Finally, neuronal signaling involves the conversion of electrical impulses into a chemical signal. Cells receive signals through a receptor, which can be an integral membrane protein or can reside inside the cell.

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once. Cells can signal to each other in various ways. A signal that must be relayed to the entire body is most efficiently sent by __________________ cells, which produce hormones that are carried throughout the body through the bloodstream. On the other hand, __________________ methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events. During __________________ signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells. Finally, __________________ signaling involves the conversion of electrical impulses into a chemical signal. Cells receive signals through a __________________, which can be an integral membrane protein or can reside inside the cell. amplification G protein phosphorylation contact-dependent K + channel receptor endocrine neuronal target epithelial paracrine

Cells can signal to each other in various ways. A signal that must be relayed to the entire body is most efficiently sent by endocrine cells, which produce hormones that are carried throughout the body through the bloodstream. On the other hand, contact-dependent methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events. During paracrine signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells. Finally, neuronal signaling involves the conversion of electrical impulses into a chemical signal. Cells receive signals through a receptor, which can be an integral membrane protein or can reside inside the cell.

For each of the following sentences, select the best word or phrase from the list below to fill in the blanks. Not all words or phrases will be used; each word or phrase should be used only once. G-protein-coupled receptors (GPCRs) all have a similar structure with __________________ transmembrane domains. When a GPCR binds an extracellular signal, an intracellular G protein, composed of __________________ subunits, becomes activated. __________________ of the G-protein subunits are tethered to the plasma membrane by short lipid tails. When unstimulated, the α subunit is bound to __________________, which is exchanged for __________________ on stimulation. The intrinsic __________________ activity of the α subunit is important for inactivating the G protein. __________________ inhibits this activity of the α subunit, thereby keeping the subunit in an active state. adenylyl cyclase cholera toxin GTPase AMP diacylglycerol phosphodiesterase ATP five seven ATPase four three Ca 2+ GDP twelve cAMP GTP two

G-protein-coupled receptors (GPCRs) all have a similar structure with seven transmembrane domains. When a GPCR binds an extracellular signal, an intracellular G protein, composed of three subunits, becomes activated. Two of the G-protein subunits are tethered to the plasma membrane by short lipid tails. When unstimulated, the α subunit is bound to GDP, which is exchanged for GTP on stimulation. The intrinsic GTPase activity of the α subunit is important for inactivating the G protein. Cholera toxin inhibits this activity of the α subunit, thereby keeping the subunit in an active state.

Match the class of cell-surface receptor with the best description of its function. Not all descriptors will be used. G-protein-coupled receptors ______ ion-channel-coupled receptors ______ enzyme-coupled receptors ______ A. alter the membrane potential directly by changing the permeability of the plasma membrane B. signal by opening and closing in a ligand-independent manner C. must be coupled with intracellular monomeric GTP-binding proteins D. all receptors of this class are polypeptides with seven transmembrane domains E. discovered for their role in responding to growth factors in animal cells

G-protein-coupled receptors ___D___ ion-channel-coupled receptors ___A___ enzyme-coupled receptors ___E___

Name the three main classes of cell-surface receptors.

Ion-channel-linked receptors; G-protein-linked receptors; enzyme-linked receptors.

How do cell surface receptors work?

Peptide, protein, and small hydrophilic signal molecules bind cell- surface receptor transmembrane proteins. The membrane receptor generates a new intracellular signal passes from 1 intracellular signaling molecule to another, ultimately activating enzymes, altering the cytoskeleton, altering gene expression.

Cellular signal molecules include:

Proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, dissoved gases, etc.

Parasympathetic nerves to the SA node of the hear do what?

Release ach, bind to GPCR which activates the G protein Gi. The beta gamma complex then binds to the intracellular face of a K+ channel and opens the channel which decreases heart rate. The alpha subunit hydrolyzes GTP and becomes inactive

Why do some signals take hours?

Requires upregulation of gene expression, and gene product modification, etc.

Can signaling through the steroid hormone/steroid hormone receptor pathway lead to amplification of the original signal? If so, how?

Since the interactions of the signal molecule with its receptor and of the activated receptor with its gene are both one-to-one, there is no amplification in this part of the signaling pathway. The signal can, however, be amplified when the target gene is transcribed, since multiple copies of mRNA are usually produced from a gene once it has been switched on, and multiple copies of protein can be made from each mRNA molecule.

Activated GPCRs activate G proteins by reducing the strength of binding of GDP to the α subunit of the G protein, allowing GDP to dissociate and GTP (which is present at much higher concentrations in the cell than GDP) to bind in its place. How would the activity of a G protein be affected by a mutation that reduces the affinity of the α subunit for GDP without significantly changing its affinity for GTP?

The mutant G protein would be constantly active. Each time the α subunit hydrolyzed GTP to GDP, the GDP would dissociate spontaneously, allowing GTP to bind and reactivate the α subunit, especially because the intracellular concentration of GTP is higher than that of GDP. Normally, GDP is tightly bound by the α subunit, which keeps the G protein in its inactive state until interaction with an appropriate activated GPCR stimulates the release of GDP.

Activated G-protein-linked receptors activate G proteins by reducing the strength of GDP binding to the α subunit of the G protein, allowing GDP to dissociate and GTP, which is present at much higher concentrations, to bind. How do you suppose the activity of a G protein would be affected by a mutation that causes the affinity of the α subunit for GDP to be reduced without significantly changing its affinity for GTP?

The mutant G protein would be constantly active. Each time the α subunit hydrolyzed GTP to GDP, the GDP would spontaneously dissociate, allowing GTP to bind and reactivate the α subunit, especially because the intracellular concentration of GTP is higher than the intracellular concentration of GDP. Normally, GDP is tightly bound by the α subunit, which keeps the G protein in its inactive state until release of GDP is stimulated by interaction with an appropriate activated G-protein-linked receptor.

Explain why the signal molecules used in neuronal signaling work at a longer range than those used in contact-dependent signaling.

The neurotransmitter released from a neuron in neuronal signaling must diffuse across the synaptic cleft to reach receptors on the target cell. In contrast, in contact-dependent signaling, the signal molecule is attached to the plasma membrane of the signaling cell and interacts with receptors located on the plasma membrane of the receiving cell; thus, the cells must be in direct contact for this type of signaling to occur.

Intracellular steroid hormone receptors have binding sites for a signaling molecule and a DNA sequence. How is it that the same steroid hormone receptor, which binds to a specific DNA sequence, can regulate different genes in different cell types?

The specific genes regulated in response to an activated steroid hormone receptor depends not only on the genes having the appropriate DNA sequence for binding the receptor but also on a variety of other nuclear proteins that influence gene expression, some of which vary between different cell types.

Rank the following types of cell signaling from 1 to 4, with 1 representing the type of signaling in which the signal molecule travels the least distance and 4 the type of signaling in which the signal molecule travels the largest distance. ______ paracrine signaling ______ contact-dependent signaling ______ neuronal signaling ______ endocrine signaling

____3__ paracrine signaling ____1__ contact-dependent signaling ____2__ neuronal signaling ____4__ endocrine signaling

Which of the following statements about molecular switches is false? (a) Phosphatases remove the phosphate from GTP on GTP-binding proteins, turning them off. (b) Protein kinases transfer the terminal phosphate from ATP onto a protein. (c) Serine/threonine kinases are the most common types of protein kinase. (d) A GTP-binding protein exchanges its bound GDP for GTP to become activated.

a

Which of the following statements is true? (a) Extracellular signal molecules that are hydrophilic must bind to a cell-surface receptor so as to signal a target cell to change its behavior. (b) To function, all extracellular signal molecules must be transported by their receptor across the plasma membrane into the cytosol. (c) A cell-surface receptor capable of binding only one type of signal molecule can mediate only one kind of cell response. (d) Any foreign substance that binds to a receptor for a normal signal molecule will always induce the same response that is produced by that signal molecule on the same cell type.

a

You are interested in cell-size regulation and discover that signaling through a GPCR called ERC1 is important in controlling cell size in embryonic rat cells. The G protein downstream of ERC1 activates adenylyl cyclase, which ultimately leads to the activation of PKA. You discover that cells that lack ERC1 are 15% smaller than normal cells, while cells that express a mutant, constitutively activated version of PKA are 15% larger than normal cells. Given these results, which of the following treatments to embryonic rat cells should lead to smaller cells? (a) addition of a drug that causes cyclic AMP phosphodiesterase to be hyperactive (b) addition of a drug that prevents GTP hydrolysis by Gα (c) addition of a drug that activates adenylyl cyclase (d) addition of a drug that mimics the ligand of ERC1

a

Which of the following statements are TRUE? (a) All hydrophilic signaling molecules bind to cell-surface receptors that contain at least one membrane-spanning domain. (b) All extracellular signaling molecules are transported across the plasma membrane into the cytosol by their receptor. (c) A cell-surface receptor capable of binding only one natural ligand can mediate only one kind of response. (d) Cells having the same set of receptors can respond in different ways to the same ligand molecules. (e) Foreign substances that occupy receptor sites normally bound by signal molecules always induce the same response that is produced by the natural ligand.

a and d

The extracellular signal may have what?

a variety of effects determined by the receptor and the intracellular machinery it regulates

Match the target of the G protein with the appropriate signaling outcome. adenylyl cyclase ________ A. cleavage of inositol phospholipids ion channels _________ B. increase in cAMP levels phospholipase C _________ C. changes in membrane potential

adenylyl cyclase ___B_____ ion channels ___C_____ phospholipase C ___A_____

How many types of mammalian G proteins are there?

approximately 20, each activated by a particular set of cell-surface receptors

Acetylcholine is a signaling molecule that elicits responses from heart muscle cells, salivary gland cells, and skeletal muscle cells. Which of the following statements is false? (a) Heart muscle cells decrease their rate and force of contraction when they receive acetylcholine, whereas skeletal muscle cells contract. (b) Heart muscle cells, salivary gland cells, and skeletal muscle cells all express an acetylcholine receptor that belongs to the transmitter-gated ion channel family. (c) Active acetylcholine receptors on salivary gland cells and heart muscle cells activate different intracellular signaling pathways. (d) Heart muscle cells, salivary gland cells, and skeletal muscle cells all respond to acetylcholine within minutes of receiving the signal.

b

When a signal needs to be sent to most cells throughout a multicellular organism, the signal most suited for this is a ___________. (a) neurotransmitter. (b) hormone. (c) dissolved gas. (d) scaffold.

b

Which of the following statements is true? (a) Because endocrine signals are broadcast throughout the body, all cells will respond to the hormonal signal. (b) The regulation of inflammatory responses at the site of an infection is an example of paracrine signaling. (c) Paracrine signaling involves the secretion of signals into the bloodstream for distribution throughout the organism. (d) The axons of neurons typically signal target cells using membrane-bound signaling molecules that act on receptors in the target cells.

b

Foreign substances like nicotine, morphine, and menthol exert their initial effects by _____. (a) killing cells immediately, exerting their physiological effects by causing cell death. (b) diffusing through cell plasma membranes and binding to transcription factors to change gene expression. (c) interacting with cell-surface receptors, causing the receptors to transduce signal inappropriately in the absence of the normal stimulus. (d) removing cell-surface receptors from the plasma membrane.

c

The following happens when a G-protein-coupled receptor activates a G protein. (a) The β subunit exchanges its bound GDP for GTP. (b) The GDP bound to the α subunit is phosphorylated to form bound GTP. (c) The α subunit exchanges its bound GDP for GTP. (d) It activates the α subunit and inactivates the βγ complex.

c

The lab you work in has discovered a previously unidentified extracellular signal molecule called QGF, a 75,000-dalton protein. You add purified QGF to different types of cells to determine its effect on these cells. When you add QGF to heart muscle cells, you observe an increase in cell contraction. When you add it to fibroblasts, they undergo cell division. When you add it to nerve cells, they die. When you add it to glial cells, you do not see any effect on cell division or survival. Given these observations, which of the following statements is most likely to be true? (a) Because it acts on so many diverse cell types, QGF probably diffuses across the plasma membrane into the cytoplasm of these cells. (b) Glial cells do not have a receptor for QGF. (c) QGF activates different intracellular signaling pathways in heart muscle cells, fibroblasts, and nerve cells to produce the different responses observed. (d) Heart muscle cells, fibroblasts, and nerve cells must all have the same receptor for QGF.

c

The local mediator nitric oxide stimulates the intracellular enzyme guanylyl cyclase by (a) way of a G-protein-mediated mechanism. (b) way of a receptor tyrosine kinase. (c) diffusing into cells and stimulating the cyclase directly. (d) way of a cell-surface receptor linked to an intracellular signaling pathway. (e) activation of intracellular protein kinases.

c

The local mediator nitric oxide stimulates the intracellular enzyme guanylyl cyclase by ________________. (a) activating a G protein. (b) activating a receptor tyrosine kinase. (c) diffusing into cells and stimulating the cyclase directly. (d) activating an intracellular protein kinase.

c

All members of the steroid hormone receptor family (a) are cell-surface receptors. (b) do not undergo conformational change. (c) are found only in the cytoplasm. (d) interact with signal molecules that diffuse through the plasma membrane. (e) regulate sexual development.

d

All members of the steroid hormone receptor family __________________. (a) are cell-surface receptors. (b) do not undergo conformational changes. (c) are found only in the cytoplasm. (d) interact with signal molecules that diffuse through the plasma membrane.

d

During nervous-system development in Drosophila, the membrane-bound protein Delta acts as an inhibitory signal to prevent neighboring cells from developing into neuronal cells. Delta is involved in ______________ signaling. (a) endocrine (b) paracrine (c) neuronal (d) contact-dependent

d

The length of time a G protein will signal is determined by _______. (a) the activity of phosphatases that turn off G proteins by dephosphorylating Gα. (b) the activity of phosphatases that turn GTP into GDP. (c) the degradation of the G protein after Gαseparates from Gβγ (d) the GTPase activity of Gα

d

When a trimeric G protein is activated by a cell-surface receptor (a) the β subunit exchanges its bound GDP for GTP. (b) the GDP bound to the α subunit is phosphorylated to form bound GTP. (c) it dissociates into a free β subunit and an αγ subunit. (d) the α subunit exchanges its bound GDP for GTP. (e) it dissociates into an active α subunit and an inactive βγ subunit.

d

Which of the following statements about G-protein-coupled receptors (GPCRs) is false? (a) GPCRs are the largest family of cell-surface receptors in humans. (b) GPCRs are used in endocrine, paracrine, and neuronal signaling. (c) GPCRs are found in yeast, mice, and humans. (d) The different classes of GPCR ligands (proteins, amino acid derivatives, or fatty acids) bind to receptors with different numbers of transmembrane domains.

d

Which of the following statements is false? (a) Nucleotides and amino acids can act as extracellular signal molecules. (b) Some signal molecules can bind directly to intracellular proteins that bind DNA and regulate gene transcription. (c) Some signal molecules are transmembrane proteins. (d) Dissolved gases such as nitric oxide (NO) can act as signal molecules, but because they cannot interact with proteins they must act by affecting membrane lipids.

d

Name the three main classes of cell-surface receptor.

ion-channel-coupled receptors; G-protein-coupled receptors; enzyme-coupled receptors

What is nitric oxide converted into?

nitrates and nitrites by reacting with O2 and H2O outside cells (half-life=5-10 seconds)

What do endothelial cells lining blood vessels do?

produce NO, causes smooth muscle to relax (vasodilation)

How does stimulation of GPCRs work?

signal binds, receptor protein changes conformation, activates G protien (trimeric, alpha, beta, gamma, alpha and gamma are tethered to the plasma membrane by lipid tails) on cytosolic surface, unactivated alpha has GDP bound, when signal molecule binds causes it to exchange GDP for GTP, and then releases beta or beta and gamma to activate target proteins.

What is nitric oxide?

synthesized from the amino acid arginine, diffuses from site of origin across into neighboring cells