Module 5 Cell Signaling: 2 Signaling through G-Protein-Coupled Receptors Flashcards
are the largest family of cell-surface receptors that mediate responses to external signals, including sight, smell, taste, and cellular communication.
G-protein-coupled receptors (GPCRs)
G-protein-coupled receptors (GPCRs) have a single __ that crosses the lipid bilayer __times, forming a __ structure.
- polypeptide chain
- seven
- cylindrical
Meanings of GDP and GTP
- guanosine triphosphate (GTP)
- guanosine diphosphate (GDP)
G-protein-coupled receptors (GPCRs) use G-proteins, specifically __, to relay signals from outside the cell to internal pathways.
trimeric GTP-binding proteins
What are the subunits of a G-protein, and their function in an unstimulated state? (3)
- proteins have three subunits: α, β, and γ.
- In the unstimulated state, the α subunit is bound to GDP, keeping the G-protein inactive.
Upon activation, GPCR acts as a __(__), causing the α subunit to release GDP, bind GTP, and undergo conformational changes.
guanine nucleotide exchange factor (GEF)
Upon activation, GPCR acts as a guanine nucleotide exchange factor (GEF), causing the __ subunit to release __, bind __, and undergo conformational changes.
- α
- GDP
- GTP
GTP binding causes the __ subunit to dissociate from the __ pair, allowing both the __ to interact with target proteins.
- Gα
- Gβγ
- Gα subunit and Gβγ complex
The α subunit is a GTPase and becomes inactive when it __ __ to __, often with the help of RGS (__) proteins.
- hydrolyzes GTP to GDP
- regulator of G-protein signaling
a large superclass of structurally and mechanistically diverse hydrolytic enzymes, which catalyze the conversion of guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and inorganic phosphate (Pi).
GTPases
act as GTPase-activating proteins (GAPs), accelerating GTP hydrolysis in the α subunit to help turn off G-protein-mediated responses.
RGS proteins (regulator G-protein signaling)
a second messenger that relays signals from extracellular molecules, such as hormones, to the cell’s interior, leading to various cellular responses.
Cyclic AMP (cAMP)/ Cyclic Adenosine Monophosphate
__ synthesizes cAMP from ATP, while __ degrade it, maintaining balance in cAMP levels.
- Adenylyl cyclase
- cyclic AMP phosphodiesterases
G proteins, such as __(__) and __(__), control the activity of adenylyl cyclase, thereby influencing the levels of cAMP in the cell.
- Gs (stimulatory)
- Gi (inhibitory)
What effect does the Gs protein have on adenylyl cyclase?
activates adenylyl cyclase, increasing the production of cAMP
What is the function of the Gi protein in cAMP regulation?
suppresses adenylyl cyclase activity, decreasing cAMP production.
__ causes ADP ribosylation of the Gs α subunit, keeping it active by preventing GTP hydrolysis, leading to excessive cAMP production and severe diarrhea.
Cholera toxin
Cholera toxin causes __ of the Gs α subunit, keeping it active by preventing __, leading to excessive cAMP production. The sustained increase in cAMP causes ion and water efflux in __ cells, resulting in severe __ typical of cholera.
- ADP ribosylation
- GTP hydrolysis
- intestinal
- diarrhea
__ ADP-ribosylates the Gi α subunit, locking it in the inactive GDP-bound state, which disrupts its ability to inhibit adenylyl cyclase.
Pertussis toxin
Pertussis toxin __ the Gi α subunit, locking it in the __, which disrupts its ability to inhibit adenylyl cyclase.
- ADP-ribosylates
- inactive GDP-bound state
When cAMP levels rise, different cell types, such as fat cells, may break down __ into __, among other responses.
- triglycerides
- fatty acids
Some Hormone-induced Cell Responses Mediated by Cyclic AMP: (9)
Given the target tissues, provide the hormones and their major responses.
1) Thyroid gland
2) Adrenal cortex
3) Ovary
4) Muscle
5) Bone
6) Heart
7) Liver
8) Kidney
9) Fat
Target tissue / Hormone / Major response
1) Thyroid gland / Thyroid-stimulating hormone (TSH)/Thyroid hormone synthesis and secretion
2) Adrenal cortex / Adrenocorticotrophic hormone (ACTH) / Cortisol secretion
3) Ovary / Luteinizing hormone (LH) / Progesterone secretion
4) Muscle / Epinephrine / Glycogen breakdown
5) Bone / Parathyroid hormone / Bone resorption
6) Heart / Epinephrine / Increase in heart rate and force of contraction
7) Liver / Glucagon / Glycogen breakdown
8) Kidney / Vasopressin / Water resorption
9) Fat / Epinephrine, ACTH, glucagon, TSH / Triglyceride breakdown
What enzyme does cAMP primarily activate to exert its effects in animal cells?
Cyclic-AMP-dependent protein kinase (PKA)
What amino acids does PKA phosphorylate on target proteins? (2)
Specific serines or threonines.
In the inactive state, PKA consists of a complex of two __ subunits and two __ subunits.
- catalytic
- regulatory
cAMP activates PKA: cAMP binds to the __ subunits of PKA, causing them to alter their conformation and dissociate from the __ subunits.
- regulatory
- catalytic
PKA phosphorylates the __ protein, which then recruits this protein to stimulate __ of target genes containing the cyclic AMP response element (CRE).
- CRE-binding (CREB) [cAMP-response element binding protein]
- transcription
What long-term cellular process is thought to be influenced by CREB activation in the brain?
Learning and memory.
Some Cell Responses in Which GPCRs Activate PLCβ: (4)
Given the target tissues, provide each of their signal molecule and major response.
1. Liver
2. Pancreas
3. Smooth muscle
4. Blood platelets
Target tissue / Signal molecule / Major response
1) Liver / Vasopressin / Glycogen breakdown
2) Pancreas / Acetylcholine / Amylase secretion
3) Smooth muscle / Acetylcholine / Muscle contraction
4) Blood platelets / Thrombin / Platelet aggregation
Which enzyme is activated by G proteins in the phospholipase C-β (PLCβ) pathway?
plasma membrane-bound enzyme phospholipase C-β (PLCβ)
Which G protein activates phospholipase C-β?
Gq
What are the two main products of Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) cleavage by phospholipase C-β? (2)
- Inositol 1,4,5-triphosphate (IP3)
- diacylglycerol (DAG)
As a second messenger, __ signaling molecule diffuses through the cytosol to the endoplasmic reticulum (ER), where it binds to IP3-gated Ca²⁺-release channels, increasing cytosolic Ca²⁺ levels.
various cellular processes, including muscle contraction, neurotransmitt
inositol phosphate (IP3)
In the PLCβ pathway, __ remains in the plasma membrane and activates protein kinase C (PKC), which requires Ca²⁺ for full activation.
diacylglycerol (DAG)
The rise in Ca²⁺ helps translocate __ to the plasma membrane, where it is activated by Ca²⁺, DAG, and phosphatidylserine.
protein kinase C (PKC)
A G-protein called __ activates a guanine nucleotide exchange factor (GEF) that activates a __, regulating the actin cytoskeleton.
- G12
- Rho-family GTPase
G proteins can directly activate or inactivate __ in the plasma membrane, affecting cell excitability.
ion channels
__ activates Gi proteins, opening K+ channels in heart muscle cells, which slows down the heart rate.
Acetylcholine
__ activate olfactory-specific binding G protein (Golf) proteins, which increase cyclic AMP (cAMP) to open ion channels and generate a signal. It activates adenylyl cyclase.
Olfactory receptors
Olfactory receptors activate __(__) proteins, which increase cyclic AMP (cAMP) to open ion channels and generate a signal. It activates adenylyl cyclase.
olfactory-specific binding G protein (Golf)
How many olfactory receptors are there in humans?
Approximately 350 olfactory receptors.
activate specific olfactory receptors involved in behavioral communication.
pheromones
What type of cells operate in bright light and is responsible for color vision?
Cone photoreceptors (cones)
What type of cells operate in dim light and is responsible for noncolor vision?
rod photoreceptors (rods)
What happens to cyclic GMP levels in rod cells when exposed to light?
decreases cyclic GMP levels, closing cation channels and causing hyperpolarization.
- When light hits rhodopsin in rod cells, retinal changes from cis to trans, activating rhodopsin. This activates the G-protein transducin, which in turn activates phosphodiesterase. PDE decreases cyclic GMP (cGMP) levels, leading to the closure of cyclic cation channels, hyperpolarizing the cell and reducing neurotransmitter release, signaling the presence of light.
a GPCR, is activated by light and alters the conformation of the G protein transducin, initiating the visual signal.
Rhodopsin
What enzyme breaks down cyclic GMP in response to light? It is activated by transducing and hydrolyzes cyclic GMP in rod cells.
Cyclic GMP phosphodiesterase
__ phosphorylates rhodopsin, reducing its ability to activate transducing.
Rhodopsin kinase
__ binds to phosphorylated rhodopsin, inhibiting its activity and helping terminate the light response.
Phototransduction in Rod Cells
Arrestin
__ binds to cation channels, keeping them open and allowing ion influx to maintain depolarization.
Phototransduction in Rod Cells
Cyclic GMP
Rods adapt to changes in light intensity through __ mechanisms, including rhodopsin deactivation and cyclic GMP replenishment, allowing quick adaptation.
negative feedback
It is a stack of discs in rod cells containing cyclic-GMP-gated cation channels essential for vision in dim light.
phototransduction apparatus
What happens to cyclic GMP in rod cells when exposed to light?
Light-activated rhodopsin changes the conformation of transducin (Gt), activating cyclic GMP phosphodiesterase, which hydrolyzes cyclic GMP, causing its levels to fall.
These channels remain open in the dark due to cyclic GMP binding; they close when cyclic GMP levels drop, leading to cell hyperpolarization.
channel and its location
cyclic-GMP-gated cation channels in the phototransduction apparatus
What is the main function of the Gs family of heterotrimeric G proteins?
Activates adenylyl cyclase and Ca²⁺ channels.
Which G protein is part of the Gs family and plays a role in olfactory sensory neurons?
what G protein and its definition
Olfactory G-protein (Golf); it activates adenylyl cyclase in olfactory sensory neurons.
What are the functions of the Gi family of heterotrimeric G proteins?
Inhibits adenylyl cyclase and activates K⁺ channels (by the βγ subunits).
Which G protein in the Gi family is responsible for activating cyclic GMP phosphodiesterase in vertebrate rod photoreceptors?
Gt (transducin)
What is the main function of the Gq family of heterotrimeric G proteins?
Activates phospholipase C-β.
What does the G12/13 family of G proteins do?
Activates Rho family monomeric GTPases via Rho GEF to regulate the actin cytoskeleton.
- a small, hydrophobic gas that readily crosses the plasma membrane to signal nearby cells.
- In mammals, it relaxes smooth muscle in blood vessel walls, leading to vessel dilation.
Nitric oxide (NO)
How acetylcholine affect nitric oxide synthesis:
Acetylcholine activates a GPCR on endothelial cells, leading to __ synthesis and __ release, which stimulates NO production.
- IP3 (Inositol triphosphate/inositol 1,4,5- triphosphate)
- Ca²⁺
How nitric oxide (NO) affects neighboring cells:
NO diffuses from __ cells into neighboring smooth muscle cells, causing __ of these muscles.
- endothelial
- relaxation
What enzymes produce nitric oxide (NO) from arginine?
NO synthases (NOS) enzymes
How does nitric oxide (NO) influence guanylyl cyclase?
in muscle function
NO binds to iron in guanylyl cyclase, increasing cyclic GMP levels, which leads to muscle relaxation.
A pathway that depend on relay chains of intracellular signaling proteins and second messengers.
GPCR-triggered intracellular signaling pathways
How do relay chains of signaling proteins amplify responses to extracellular signals?
they amplify cascade of stimulatory signals
What are the three modes of adaptation for GPCRs? (3)
- Receptor sequestration
- Receptor down-regulation
- Receptor inactivation
receptor becomes altered so that it can no longer interact with G proteins
what mode of adaptation?
receptor inactivation
receptor is temporarily internalized to the cell interior, preventing access to its ligand.
what mode of adaptation?
receptor sequestration
It involves the destruction of receptors in lysosomes after they have been internalized.
what mode of adaptation?
receptor down-regulation
- prevents the activated receptor from interacting with G proteins and serves as an adaptor protein for endocytosis.
- facilitates receptor-mediated endocytosis.
arrestine
