Module 7.1 GPCRs 1

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Questions and Answers

What is the structure of a GPCR like the oxytocin receptor?

It has an extracellular N-terminus and an intracellular C-terminus.

It has a sequence of 7 beta sheets that cross the membrane.

It has an intracellular N-terminus and an extracellular C-terminus.

It has a sequence of 7 coiled domains that cross the membrane. (correct)

How many genes are there in the GPCR superfamily?

Approximately 1000

Approximately 500

Approximately 1200

Approximately 800 (correct)

What happens when the heterotrimeric G-protein is activated?

The GDP gets phosphorylated and downstream signaling effectors are inhibited.

The GDP gets hydrolyzed and downstream signaling effectors are activated. (correct)

The GDP gets phosphorylated and upstream signaling effectors are activated.

The GDP gets hydrolyzed and upstream signaling effectors are activated.

What are orphan receptors?

Receptors to which the ligand is unknown. Signup and view all the answers

What is the function of the N-terminus in a GPCR?

It is the extracellular part of the protein chain. Signup and view all the answers

Which type of signaling molecules do GPCRs respond to?

Endogenous small molecules, hormones, and neurotransmitters. Signup and view all the answers

What is the structure of a heterotrimeric G-protein?

It has 3 subunits: alpha, beta, gamma. Signup and view all the answers

Which GRK is exclusively expressed in photoreceptors in the retina?

GRK1 Signup and view all the answers

Which GRK is found in all cells and is expressed everywhere in the body?

GRK2 Signup and view all the answers

Which GRK's targeting is controlled by G beta gamma and PIP2?

GRK2 and GRK3 Signup and view all the answers

Which GRK is always at the membrane?

GRK4 Signup and view all the answers

Which kinase can modulate GRK activity as mentioned in the text?

PKA Signup and view all the answers

Which desensitization pathway involves the activation of second messenger kinases as the first step?

Heterologous desensitization Signup and view all the answers

How many GRK phosphorylation sites are there in beta2 adrenergic receptors?

11 Signup and view all the answers

At low concentrations of hormones, which kinase's activation leads to desensitization?

PKA Signup and view all the answers

At high agonist concentrations, which kinases are involved in the phosphorylation of beta2 adrenergic receptors?

PKA and GRK (BARK) Signup and view all the answers

Which receptor complex undergoes lysosomal degradation?

AM1 receptor complex Signup and view all the answers

What is the quality control mechanism for GABAB receptor formation?

ER retention signal in the C-terminal tail of GABAB1 and dimerization with GABAB2 Signup and view all the answers

How is the cell surface expression of somatostatin receptor subtype sst5 regulated?

By recycling/intracellular storage of receptors Signup and view all the answers

What regulates the cell surface expression and targeting of GPCRs?

Different mechanisms with constitutive expression at the cell surface Signup and view all the answers

What is extensively studied and serves as a model for GPCR function?

Betanergic (B1) receptors Signup and view all the answers

What is involved in the GPCR desensitization process?

Homologous and heterologous desensitization, and the role of arrestins in signal termination and desensitization Signup and view all the answers

What initiates downstream signaling and desensitization of GPCRs?

The binding of a ligand Signup and view all the answers

Which organelle is involved in the transport, modification, and packaging of secretory and transmembrane proteins for secretion?

Golgi apparatus Signup and view all the answers

What is the role of RAMPs in the regulation of GPCRs?

Act as chaperones, pharmacology switches, signaling switches, and trafficking switches for GPCRs Signup and view all the answers

Which receptor does RAMP1 bring to the cell surface, enabling it to function as a receptor for CGRP?

Calcitonin Receptor-Like Receptor (CLR) Signup and view all the answers

What is the function of RAMP2 and RAMP3 binding to CLR?

Enable CLR to function as a receptor for AM1 and AM2 Signup and view all the answers

What is the primary role of RAMPs in diversifying GPCR function and regulation?

Cause different binding specificity or different signaling properties in GPCRs Signup and view all the answers

What happens to cell-surface receptors after endocytosis?

They are either recycled back to the membrane or sorted to lysosomes for degradation Signup and view all the answers

What is the impact of RAMPs interacting with specific GPCRs such as CTR and CLR?

Altering their function and specificity for different hormones Signup and view all the answers

Study Notes

GPCR Activation, Trafficking, and RAMPs

GPCRs undergo biosynthesis in the secretory pathway and are transported to the Golgi apparatus for further processing before targeting the plasma membrane.
Endocytosis removes cell-surface receptors, which are then either recycled back to the membrane or sorted to lysosomes for degradation.
The Golgi apparatus is a dynamic organelle involved in the transport, modification, and packaging of secretory and transmembrane proteins for secretion.
RAMPs play essential roles in the pharmacology and regulation of GPCRs, modulating their function and trafficking.
RAMPs are highly conserved and can alter GPCR function, leading to the generation of diverse GPCR types, reflecting the "economy principle" in evolution.
RAMPs act as chaperones, pharmacology switches, signaling switches, and trafficking switches for GPCRs, influencing their appearance, ligand specificity, signaling properties, and internalization.
RAMPs interact with specific GPCRs such as Calcitonin Receptor (CTR) and Calcitonin Receptor-Like Receptor (CLR), altering their function and specificity for different hormones.
RAMP1 brings CLR to the cell surface, enabling it to function as a receptor for CGRP, a neuropeptide involved in pain transmission.
RAMP2 and RAMP3 binding to CLR lead to its function as a receptor for AM1 and AM2, hormones involved in blood pressure regulation and kidney function, respectively.
RAMPs also interact with CTR, altering its function to become a receptor for amylin, a hormone involved in glucose regulation, and VPAC1-R, a regulator of blood pressure.
In most cases, RAMPs cause different binding specificity or different signaling properties in GPCRs, highlighting their role in diversifying GPCR function and regulation.
The study of RAMPs and their interactions with GPCRs provides valuable insights into the molecular mechanisms underlying GPCR activation, trafficking, and pharmacology.

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Test your knowledge of GPCR activation, trafficking, and RAMPs with this quiz. Explore the essential roles of RAMPs in modulating GPCR function and trafficking, as well as their interactions with specific GPCRs. Gain insights into the molecular mechanisms underlying GPCR pharmacology and regulation.