MODULE 7 CONDENSED
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Questions and Answers

What is the structure of a GPCR?

  • 4 transmembrane protein with N term in extracellular part and C term in intracellular
  • 5 transmembrane protein with N term in intracellular part and C term in extracellular
  • 6 transmembrane protein with N term in intracellular part and C term in extracellular
  • 7 transmembrane protein with N term in extracellular part and C term in intracellular (correct)

    • How many receptors within the GPCR SuperFamily have unknown function?

  • More than 800
  • More than 1000
  • More than 400
  • More than 600 (correct)

    • What happens to GDP when a heterotrimeric G protein is activated?

  • It hydrolyzes to GTP (correct)
  • It is phosphorylated
  • It remains unchanged
  • It dissociates from the alpha subunit

    • What are the modes of internalization for GPCRs?

    <p>Clathrin-Coated Endocytosis and Caveolin Endocytosis</p> Signup and view all the answers

    Which part of the Golgi Apparatus receives newly synthesized proteins?

    <p>$Cis$</p> Signup and view all the answers

    What are RAMPs in relation to GPCRs?

    <p>Receptor Activity-Modifying Proteins, bind to GPCR and alter function</p> Signup and view all the answers

    What are the types of signaling initiation for GPCRs?

    <p>Photoreceptors, odours/pheromones, Calcium, light, proteins (hormone)</p> Signup and view all the answers

    Which domain of a GPCR constitutes the transmembrane portion?

    <p>Hydrophobic Lipophilic Domain</p> Signup and view all the answers

    What are the subunits of a heterotrimeric G protein?

    <p>Alpha, beta, gamma</p> Signup and view all the answers

    What are the methods of exiting Trans-Golgi Network (TGN)?

    <p>Constitutive secretion and regulated secretion</p> Signup and view all the answers

    Which type of vesicles have many similarities to GSVs and are located in the pituitary gland to regulate the activity of the adrenal gland?

    <p>Regulated recycling vesicles</p> Signup and view all the answers

    Which type of somatostatin receptors are internalized very quickly and recycle slowly?

    <p>sst2A</p> Signup and view all the answers

    What is the pH range along the endocytotic pathway that allows lysosomes to degrade better and receptors to be separated from their ligands?

    <p>$4-5$</p> Signup and view all the answers

    Which type of GPCR receptor has low affinity for visual arrestin and does not co-localize in endosomes?

    <p>Class A</p> Signup and view all the answers

    What is the post-endocytic trafficking pathway of sst2A somatostatin receptors?

    <p>$ ext{Clathrin-coated vesicles} ightarrow ext{Endosomes} ightarrow ext{TGN} ightarrow ext{Cell surface}$</p> Signup and view all the answers

    What is the effect of Brefeldin A on SSTR2 and syntaxin-6?

    <p>Does NOT affect SSTR2 or syntaxin-6</p> Signup and view all the answers

    What happens when Class A GPCR receptors undergo ubiquitination?

    <p>RAPIDLY de-Ub, leading to fast recycling</p> Signup and view all the answers

    What is the system that allows cells to adapt to environmental changes such as those in adipose tissue, muscle, and liver?

    <p>Regulated Recycling</p> Signup and view all the answers

    What is the location of GSVLs?

    <p>Pituitary gland</p> Signup and view all the answers

    Which type of GPCR receptor has high affinity for visual arrestin and co-localizes in endosomes?

    <p>Class B</p> Signup and view all the answers

    Which RAMP binds to CLR, making it the receptor for AM1, a protein hormone with vasodilator effects?

    <p>RAMP2</p> Signup and view all the answers

    What is the receptor for CGRP, a neuropeptide modulating pain transmission?

    <p>CLR binding to RAMP1</p> Signup and view all the answers

    Which type of receptors require both wildtype isoforms for a functioning receptor at the cell surface?

    <p>GABAB receptors</p> Signup and view all the answers

    How many groups of GRKs play a role in GPCR desensitization?

    <p>Three groups</p> Signup and view all the answers

    What type of desensitization involves direct phosphorylation by GRK2, specific to the receptor?

    <p>Homologous desensitization</p> Signup and view all the answers

    Which type of receptors prefer homologous desensitization due to more sites for GRK phosphorylation?

    <p>$\beta$2 adrenergic receptors</p> Signup and view all the answers

    What is the structure of a GPCR?

    <p>Single transmembrane protein with N term in extracellular part and C term in intracellular</p> Signup and view all the answers

    How many receptors within the GPCR SuperFamily have unknown function?

    <p>Over 600</p> Signup and view all the answers

    What are the modes of internalization for GPCRs?

    <p>Clathrin-Coated Endocytosis and Caveolin Endocytosis</p> Signup and view all the answers

    What is the effect of Brefeldin A on GPCR trafficking?

    <p>It inhibits vesicle formation at the TGN</p> Signup and view all the answers

    What are RAMPs in relation to GPCRs?

    <p>They bind to GPCRs and alter their function</p> Signup and view all the answers

    What is the role of Heterotrimeric G Proteins when activated?

    <p>GDP will hydrolyze to GTP, activating downstream signaling effectors</p> Signup and view all the answers

    Which domain of a GPCR constitutes the transmembrane portion?

    <p>Hydrophobic Lipophilic Domain</p> Signup and view all the answers

    What are the parts of Golgi Apparatus in sequence from receiving newly synthesized proteins to sending them to the plasma membrane?

    <p>Cis → Medial → Trans → PM</p> Signup and view all the answers

    What are the types of signaling initiation for GPCRs?

    <p>Photoreceptors, odours/pheromones, Calcium, light, proteins (hormone)</p> Signup and view all the answers

    Which type of receptors require both wildtype isoforms for a functioning receptor at the cell surface?

    <p>Class C GPCR receptors</p> Signup and view all the answers

    Which GPCR-associated protein has four functions including chaperone, pharmacology switch, signaling switch, and trafficking switch?

    <p>RAMP</p> Signup and view all the answers

    Which GPCR receptor is closely related to the calcitonin receptor (CTP) and interacts with RAMPs?

    <p>CLR (calcitonin-like receptor)</p> Signup and view all the answers

    Which GPCR-associated protein is brought to the receptor by arrestin and stops GPCR signaling?

    <p>PDE4</p> Signup and view all the answers

    Which type of GPCR desensitization involves four steps and three groups of GRKs?

    <p>Heterologous desensitization</p> Signup and view all the answers

    Which type of somatostatin receptors exhibit different internalization and externalization responses?

    <p>$sst2A$ and $sst5$ receptors</p> Signup and view all the answers

    What is the widespread location of GABAB receptor in the body?

    <p>Central Nervous System (CNS)</p> Signup and view all the answers

    What are the two isoforms of the GABAB receptor?

    <p>GABAB1 and GABAB2</p> Signup and view all the answers

    What are the two functions of arrestins in relation to GPCR desensitization?

    <p>Stopping signaling by binding to GPCR, direct binding to clathrin-coated pits</p> Signup and view all the answers

    What is the enzyme that stops GPCR signaling by interacting with arrestin?

    <p>PDE4</p> Signup and view all the answers

    What structure causes invaginations of the plasma membrane and is involved in GPCR internalization?

    <p>Caveolae</p> Signup and view all the answers

    What is the pH range along the endocytotic pathway that allows lysosomes to degrade better and receptors to be separated from their ligands?

    <p>pH 4-5</p> Signup and view all the answers

    Which type of GPCR receptor has low affinity for visual arrestin and does not co-localize in endosomes?

    <p>Class A</p> Signup and view all the answers

    What is the post-endocytic trafficking pathway of sst2A somatostatin receptors?

    <p>Clathrin-coated vesicles -&gt; Endosomes -&gt; Trans-Golgi Network (TGN) -&gt; Cell surface</p> Signup and view all the answers

    What happens when Class A GPCR receptors undergo ubiquitination?

    <p>Rapid de-ubiquitination leading to fast recycling</p> Signup and view all the answers

    What are GSVLs and where are they located?

    <p>GSV-like vesicles with many similarities to GSVs, located in the pituitary gland</p> Signup and view all the answers

    Which type of somatostatin receptors are internalized very quickly and recycle slowly?

    <p>$sst2A$</p> Signup and view all the answers

    What is the system that allows cells to adapt to environmental changes such as those in adipose tissue, muscle, and liver?

    <p>Regulated Recycling</p> Signup and view all the answers

    Which type of GPCR receptor has high affinity for visual arrestin and co-localizes in endosomes?

    <p>Class B</p> Signup and view all the answers

    What happens to GDP when a heterotrimeric G protein is activated?

    <p>It dissociates from the alpha subunit</p> Signup and view all the answers

    What is the effect of Brefeldin A on SSTR2 and syntaxin-6?

    <p>Disperses Golgi around the cell but does not affect SSTR2 or syntaxin-6</p> Signup and view all the answers

    Study Notes

    Evolution and Functions of GPCRs and RAMPs

    • RAMPs are highly conserved, with RAMP1 and RAMP3 being more closely related than RAMP2.
    • RAMPs serve as chaperones, pharmacology switches, signaling switches, and trafficking switches for GPCRs.
    • The calcitonin receptor (CTP) interacts with RAMPs and is closely related to CLR (calcitonin-like receptor).
    • CLR binds to RAMP1 and becomes the receptor for CGRP, a neuropeptide modulating pain transmission.
    • RAMP2 binds to CLR, making it the receptor for AM1, a protein hormone with vasodilator effects.
    • RAMP3 binds to CLR, making it the receptor for AM2, a hormone regulating glucose levels.
    • GABAB receptors, mediating rapid action ion channels, require both wildtype isoforms for a functioning receptor at the cell surface.
    • GPCR desensitization involves a 4-step process: resting state, stimulation, phosphorylation, and desensitization.
    • Three groups of GRKs play a role in GPCR desensitization, with different locations and domains.
    • Homologous desensitization involves direct phosphorylation by GRK2, specific to the receptor, while heterologous desensitization involves second messenger kinases.
    • Beta2 adrenergic receptors prefer homologous desensitization due to more sites for GRK phosphorylation.
    • Arrestins are key adaptor proteins in GPCR desensitization and internalization, with four types and specific functions in stopping signaling and binding to GPCR.

    Functions and Mechanisms of GPCR-Associated Proteins

    • RAMPs, highly conserved, with RAMP1 and RAMP3 more closely related than RAMP2
    • Four functions of RAMP: chaperone, pharmacology switch, signaling switch, trafficking switch
    • Calcitonin receptor (CTP) interacts with RAMPs, closely related to CLR (calcitonin-like receptor)
    • GABAB receptor, widespread in CNS, has two isoforms and a quality control mechanism
    • sst2A and sst5, somatostatin receptors, exhibit different internalization and externalization responses
    • Betanergic (B1) receptors extensively studied and used as GPCR model
    • GPCR desensitization involves four steps and three groups of GRKs
    • Homologous and heterologous desensitization of GPCRs, with beta2 adrenergic receptors preferring homologous desensitization
    • Arrestins, key adaptor proteins in GPCR desensitization and internalization, have four types
    • Arrestins have two functions: stopping signaling by binding to GPCR and direct binding to clathrin-coated pits
    • PDE4, an enzyme brought to the receptor by arrestin, stops GPCR signaling
    • Caveolae, formed by myelin, cause invaginations of the plasma membrane and are involved in GPCR internalization

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    Description

    Test your knowledge of G protein-coupled receptors (GPCRs) and heterotrimeric G proteins. Learn about the structure of GPCRs, the GPCR superfamily, hydrophobic and hydrophilic domains, and the types of signaling initiation. Explore the composition and activation of heterotrimeric G proteins.

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