G-Protein Coupled Receptors
Acetylcholine binds to a GPCR on heart muscle, making the heart beat more slowly. The activated receptor stimulates a G protein, which opens a K+ channel in the plasma membrane, as shown in Figure Q16-32. Which of the following would enhance this effect of the acetylcholine? Figure Q16-32 (a) addition of a high concentration of a nonhydrolyzable analog of GTP (b) addition of a drug that prevents the α subunit from exchanging GDP for GTP (c) mutations in the acetylcholine receptor that weaken the interaction between the receptor and acetylcholine (d) mutations in the acetylcholine receptor that weaken the interaction between the receptor and the G protein
(a) addition of high concentration of nonhydrolyzable analog of GTP
16-29 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 a-subunit exchanges its bound GDP for GTP
16-44 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. Ca2+ can trigger biological effects in cells because an unstimulated cell has an extremely __________________ concentration of free Ca2+ in the cytosol, compared with its concentration in the __________________ space and in the __________________, creating a steep electrochemical gradient. When Ca2+ enters the cytosol, it interacts with Ca2+-responsive proteins such as __________________, which also binds diacylglycerol, and __________________, which activates CaM-kinases. adenylyl cyclase endoplasmic reticulum nuclear average extracellular peroxisome Ca2+ high phospholipase C calmodulin intracellular protein kinase A colorful low protein kinase C
low extracellular endoplasmic reticulum protein kinase c calmodulin
16-40 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) addition of a drug that causes cyclic AMP phosphodiesterase to be hyperactive
16-38 Activated protein kinase C (PKC) can lead to the modification of the membrane lipids in the vicinity of the active PKC. Figure Q16-38 shows how G proteins can indirectly activate PKC. You have discovered the enzyme activated by PKC that mediates the lipid modification. You call the enzyme Rafty and demonstrate that activated PKC directly phosphorylates Rafty, activating it to modify the plasma membrane lipids in the vicinity of the cell where PKC is active; these lipid modifications can be detected by dyes that bind to the modified lipids. Cells lacking Rafty do not have these modifications, even when PKC is active. Which of the following conditions would lead to signal-independent modification of the membrane lipids by Rafty? Figure Q16-38 (a) the expression of a constitutively active phospholipase C (b) a mutation in the GPCR that binds the signal more tightly (c) a Ca2+ channel in the endoplasmic reticulum with an increased affinity for IP3 (d) a mutation in the gene that encodes Rafty such that the enzyme can no longer be phosphorylated by PKC
(a.) the expression of a constitutively active phospholipase C
16-34 During the mating process, yeast cells respond to pheromones secreted by other yeast cells. These pheromones bind GPCRs on the surface of the responding cell and lead to the activation of G proteins inside the cell. When a wild-type yeast cell senses the pheromone, its physiology changes in preparation for mating: the cell stops growing until it finds a mating partner. If yeast cells do not undergo the appropriate response after sensing a pheromone, they are considered sterile. Yeast cells that are defective in one or more components of the G protein have characteristic phenotypes in the absence and presence of the pheromone, which are listed in Table 16-34. Table Q16-34 Which of the following models is consistent with the data from the analysis of these mutants? Explain your answer. (a) α activates the mating response but is inhibited when bound to βγ (b) βγ activates the mating response but is inhibited when bound to α (c) the G protein is inactive; either free α or free βγ complex is capable of activating the mating response (d) the G protein is active; both free α and free βγ complex are required to inhibit the mating response
(b.) By (beta omega) activates the mating response but is inhibited when bound to alpha
16-35 You are interested in how cyclic-AMP-dependent protein kinase A (PKA) functions to affect learning and memory, and you decide to study its function in the brain. It is known that, in the cells you are studying, PKA works via a signal transduction pathway like the one depicted in Figure Q16-35. Furthermore, it is also known that activated PKA phosphorylates the transcriptional regulator called Nerd that then activates transcription of the gene Brainy. Which situation described below will lead to an increase in Brainy transcription? Figure Q16-35 (a) a mutation in the Nerd gene that produces a protein that cannot be phosphorylated by PKA (b) a mutation in the nuclear import sequence of PKA from PPKKKRKV to PPAAAAAV (c) a mutation in the gene that encodes cAMP phosphodiesterase that makes the enzyme inactive (d) a mutation in the gene that encodes adenylyl cyclase that renders the enzyme unable to interact with the α subunit of the G protein
(c.) a mutation in the gene that encodes cAMP phosphodiesterase that makes the enzyme inactive
16-36 Adrenaline stimulates glycogen breakdown in skeletal muscle cells by ultimately activating glycogen phosphorylase, the enzyme that breaks down glycogen, as depicted in Figure Q16-36. Figure Q16-36 Which of the following statements is false? (a) A constitutively active mutant form of PKA in skeletal muscle cells would lead to a decrease in the amount of unphosphorylated phosphorylase kinase. (b) A constitutively active mutant form of PKA in skeletal muscle cells would not increase the affinity of adrenaline for the adrenergic receptor. (c) A constitutively active mutant form of PKA in skeletal muscle cells would lead to an excess in the amount of glucose available. (d) A constitutively active mutant form of PKA in skeletal muscle cells would lead to an excess in the amount of glycogen available.
(d.) a constitutively active mutant form of PKA in skeletal muscle. Cells would lead to an excess in the amount of glycogen available
16-31 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.) the GTPase activity of Ga
16-30 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.) the different classes of GPCR ligands (proteins, amino acid derivatives, or fatty acids) bind to receptors with different number of transmembrane domains
16-27 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 Ca2+ GDP twelve cAMP GTP two
Seven Three Two alpha GDP GTP GTPase Cholera toxin
16-43 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 increase cAMP levels ion channels ___C changes in membrane potential phospholipase C ___A cleavage of inositol phospholipids