Week 29 / G-Protein-Coupled Receptor 2 Flashcards
What enzyme does Ga-GTP stimulate in the cAMP signaling pathway?
✅ Answer: Ga-GTP stimulates Adenylyl Cyclase (AC), a membrane-bound enzyme.
What is the function of Adenylyl Cyclase (AC)?
✅ Answer: AC converts ATP to cyclic AMP (cAMP).
How does an increase in cAMP affect protein kinase A (PKA)?
✅ Answer: Increased cAMP activates protein kinase A (PKA).
What is the role of activated PKA?
✅ Answer: Activated PKA phosphorylates multiple downstream effector targets, leading to a cellular response.
Besides activating PKA, how else can cAMP affect the cell?
✅ Answer: cAMP can modulate the activity of Guanine Exchange Factors (GEFs) and ion channels.
What is the effect of Go-GTP on Adenylyl Cyclase (AC)?
✅ Answer: Go-GTP inhibits AC, lowering cAMP levels and reducing PKA activation.
How does Go-GTP inhibition of AC influence the cellular response?
✅ Answer: By lowering cAMP and reducing PKA activation, Go-GTP alters the downstream cellular response.
Which G-protein subunit activates Phospholipase C-β (PLCβ)?
✅ Answer: Gq/11-GTP activates Phospholipase C-β (PLCβ).
What is the function of Phospholipase C-β (PLCβ)?
✅ Answer: PLCβ catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol triphosphate (IP₃) and diacylglycerol (DAG).
What is the role of IP₃ in the signaling pathway?
✅ Answer: IP₃ acts on the endoplasmic reticulum (ER) to trigger the release of Ca²⁺ into the cytoplasm.
How does Ca²⁺ influence cellular responses?
✅ Answer: Ca²⁺ modulates the activity of Ca²⁺-dependent effector proteins (e.g., calmodulin, transcription factors), leading to a cellular response.
What is the role of DAG in the IP₃/Ca²⁺ pathway?
✅ Answer: DAG, along with increased Ca²⁺ levels, activates protein kinase C (PKC) at the cell membrane.
How does PKC contribute to the cellular response?
✅ Answer: PKC phosphorylates multiple downstream effector proteins, leading to a cellular response.
What is phosphatidylinositol-bisphosphate (PIP₂)?
✅ Answer: PIP₂ is a membrane phospholipid.
Which enzyme cleaves PIP₂, and how is it activated?
✅ Answer: Phospholipase C-β (PLCβ) cleaves PIP₂, and it is activated by Gq-GTP.
What are the two second messengers generated from PIP₂ cleavage?
✅ Answer: Inositol triphosphate (IP₃) and diacylglycerol (DAG).
Where does IP₃ function, and what does it do?
✅ Answer: IP₃ diffuses through the cytosol and triggers Ca²⁺ release from the endoplasmic reticulum (ER).
Where does DAG remain, and what is its function?
✅ Answer: DAG stays in the membrane and activates protein kinase C (PKC).
What forms the Gβγ dimer?
✅ Answer: The Gβ and Gγ subunits are tightly bound to form an obligate functional heterodimer.
How many Gβ and Gγ subunits exist in the human genome?
✅ Answer: There are 5 Gβ and 12 Gγ subunits, allowing for multiple Gβγ dimer combinations.
What modification helps localize the Gβγ dimer to the membrane?
✅ Answer: Lipid modification of the Gγ subunit facilitates membrane attachment.
What happens to the Gβγ dimer upon GPCR activation?
✅ Answer: GPCR activation leads to Ga-GTP dissociation, freeing the Gβγ dimer.
What are the key downstream effectors regulated by the free Gβγ dimer?
✅ Answer: The Gβγ dimer regulates:
Voltage-gated Ca²⁺ channels
Inwardly rectifying K⁺ channels
GPCR kinases
Phosphoinositide 3-kinases
Adenylyl cyclase
Phospholipase C-β
Which two major intracellular proteins regulate GPCR desensitization?
✅ Answer:
G protein-coupled receptor kinases (GRKs)
β-arrestins (cytoplasmic adaptor proteins)
What controls the temporal and spatial signaling of activated GPCRs?
✅ Answer: GPCR signaling is controlled by desensitization and internalization.
How does heterologous desensitization occur?
✅ Answer: PKA, PKC, and other serine/threonine (S/T) kinases phosphorylate inactive GPCRs, leading to desensitization independent of prior activation.
What is the first step in homologous desensitization?
✅ Answer: GRK docks onto the activated GPCR and phosphorylates serine and threonine residues, inhibiting G-protein activation.
What role do β-arrestins play after binding to phosphorylated GPCRs?
✅ Answer: β-arrestins sterically hinder GPCR-G protein coupling, preventing further G protein-mediated signaling.
How do β-arrestins facilitate GPCR internalization?
✅ Answer: β-arrestins couple phosphorylated GPCRs to clathrin-coated pits, promoting receptor internalization.
Where are internalized GPCRs trafficked?
✅ Answer: Internalized GPCRs are trafficked to endosomes.
What are the three possible fates of internalized GPCRs?
✅ Answer:
Recycling: Dephosphorylation by phosphatases, allowing the receptor to return to the cell surface.
Degradation: Sorting to lysosomes for degradation.
Alternative signaling: Activation of β-arrestin-dependent, G-protein-independent signaling cascades.
Why is GPCR desensitization necessary?
✅ Answer: To prevent uncontrolled signaling and ensure rapid attenuation of receptor responsiveness.
How is GPCR desensitization initiated?
✅ Answer: It begins with phosphorylation of the receptor by GPCR kinases (GRKs), followed by β-arrestin-mediated uncoupling of GPCR-G protein interactions.
What dual role do β-arrestins play in GPCR signaling?
✅ Answer:
Terminate G protein signaling by preventing further GPCR-G protein interactions.
Promote GPCR signaling by facilitating receptor internalization and acting as molecular scaffolds for signaling proteins.
How do β-arrestins contribute to alternative signaling pathways?
✅ Answer: They initiate G protein-independent GPCR signaling cascades by recruiting specific signaling proteins.
