GPCRs and G-Protein Signaling Quiz

Introduction to G Protein-Coupled Receptor Signal Transduction

• G protein-coupled receptors (GPCRs) are a large family of transmembrane receptors that play crucial roles in cell signaling.
• GPCRs are involved in diverse physiological processes and are prominent drug targets.
• Key components of a GPCR system include orthosteric sites, G-proteins, and intracellular signaling cascades.

G Protein-Coupled Receptors and their Signaling Systems

• This section aims to familiarize students with the components of the GPCR system, understand how these receptors become activated, and provide examples of systems regulated by GPCRs.
• It also touches upon physiological and pharmacological aspects.

Major Players Covered in PCL302

• Orthosteric sites are crucial for endogenous ligand binding, where many GPCR drugs bind.
• G protein-coupled receptor (GPCR) internalization and desensitization blocks G protein access.
• Additional signaling cascades are activated following receptor activation.

GPCRs are encoded by hundreds of human genes

• The number of GPCRs varies between mice and humans.
• Various groups of GPCRs exist (e.g., Rhodopsin, Frizzled, Taste Type 2, Secretin, Olfactory, etc).
• Data shows significant numbers of GPCRs encoded in both species.

GPCR Superfamily

• GPCRs are categorized into families based on their structures and function.
• A diagram showcases the relationships between different GPCR families.

GPCR Ligands

• Neurotransmitters like adrenaline, dopamine, serotonin, and glutamate, as well as GABA, are ligands.
• Peptide hormones (e.g., thyroid-stimulating hormone, parathyroid hormone) are also ligands.
• Sensory stimuli, like light, odors, salt, and sugar, can act as ligands.
• Prostaglandins and glycoprotein growth-differentiation factors are other categories of GPCR ligands.

GRVFS classification of vertebrate GPCR

• The presented table classifies GPCRs based on their characteristics and provides example receptors for each family.

Nomenclature

• GPCR stands for G-protein coupled receptors, a broad term.
• 7TM refers to the seven transmembrane domains found in many GPCR types.

GPCRs are major drug targets

• GPCRs are major targets for both protein and small molecule drugs.
• The relative proportions of drug targets for each category of GPCR are presented graphically.

Structural Features of GPCRs

• GPCRs comprise seven transmembrane domains, extracellular and intracellular loops, and terminal regions.
• Ligand binding occurs within or outside the transmembrane helices.
• G proteins interact with the inside surface of the receptor.

Secondary Structure (Class-A)

• The structure of GPCRs, particularly for Class-A receptor types (e.g. dopamine receptors), are depicted.
• Different features such as locations of glycosylation sites, palmitoylation sites, and phosphorylation sites are indicated.

Secondary Structure (β-adrenergic receptor)

• A diagram of a specific class-A GPCR, the beta-adrenergic receptor.

Class-B: Secretin Receptor

• The structure of a Secretin receptor is depicted, showing details like alpha and beta sheets and ligand-binding motifs.

Class-C: Metabotropic Glutamate Receptor

• The structural features of a Metabotropic receptor, highlighting important domains like glutamate binding site and the seven-transmembrane region.

Homomers Heterodimers of Class C GPCRs

• Illustrates the dimeric nature of some class C GPCRs.

G-Proteins, Heterotrimeric G protein structure

• Shows the structure of G-proteins—heterotrimeric components with alpha, beta, and gamma subunits.

G Protein-Coupled Receptor (GPCR) Mechanism

• Describes the general mechanism of GPCR signaling, which begins with ligand binding.

Inactivation of G Proteins

• Focuses on GTP hydrolysis as a crucial part of deactivating G proteins.

Regulators of G protein Signaling (RGS Proteins)

• RGS proteins—regulators of G protein signaling are highlighted in their function and classification.

Regional expression patterns and known transcriptional modulators of CNS-relevant RGS genes

• A table that details CNS expression patterns and potential modulators.

G protein deactivation by RGS

• Diagrams on G-protein deactivation using RGS proteins

The Family of Heterotrimeric G Proteins

• Shows the classification of heterotrimeric G proteins into families (e.g. Gs, Gi, Gq, G12).

G βy Subunits

• Presents a table detailing the various subunit types.

Effectors Regulated by G proteins, Adenylyl Cyclase

• Displays adenyl cyclase enzymes and their catalytic domains.
• Includes details on adenyl cyclase isoforms, activators, and inhibitors.

Gs and Gi Regulation of Adenylyl Cyclase

• Explains how Gs and Gi proteins regulate adenylyl cyclase activity.
• Includes diagrams illustrating the interactions

cAMP Signaling

• Outlines how cAMP regulates cellular processes through PKA activation.

Examples of cAMP-regulated systems

• Provides examples where cAMP-related mechanisms mediate specific biological responses.

Effectors Regulated by G proteins, PLC-β

• Discusses the role of PLC-β as an effector regulated by G proteins.

Inositol Phosphates

• Diagrams the inositol phosphate cycle pathway and related structures.

Stimulation of PLC by Gq

• Describes how Gq proteins regulate PLC-β activity, emphasizing the hydrolysis of PIP2 to IP3 and DAG.

Down-stream of PLC

• Details downstream effects of PLC including calcium stimulation and kinases.

PKC Family

• Presents structural aspects and activators.

Adenylyl Cyclase

• Demonstrates a visual representation of adenylyl cyclase regulation.

PLC

• Outlines the steps related to PLC activation.

Ion Channels

• Explains the basic mechanism that GPCRs have in relation to the regulation of ion channels.

GPCR Desensitization

• Explains how G-protein coupled receptors (GPCRs) are regulated following activation, particularly the inactivation mechanisms involved.

Homologous Desensitization and Down-regulation of GPCRs

• Discusses homologous desensitization and down-regulation of GPCRs.

GPCR Kinases (GRKs)

• Details GPCR Kinases (GRKs) including their structures and domains.

Putative domain architecture of the (beta)-arrestins

• Details the architecture of beta-arrestins.

Beta Arrestin as signaling effectors

• Outlines how beta-arrestins function and are involved in different cellular processes.

Multiplicité d'action des GPCRs

• Contains information on the multiple roles and signaling pathways of GPCRs.

D2-class responding neurons

• Discusses the example of a signaling network of dopamine D2 receptors.

Multidimensional Drug efficacy

• Explains how different criteria can be used to evaluate drug efficacy.

Heart Rate Regulation by Beta-Adrenergic Receptors

• This section provides specifics about how Beta-adrenergic receptors influence heart rate, including the involved components and mechanisms.

𝛽–Adrenergic Receptor Antagonists

• Lists drugs categorized as beta-adrenergic antagonists, along with their corresponding receptors and uses.

asthma

• Discusses information related to asthma including prevalence among children.

𝛽2- Selective Receptor Agonists

• Details specific agonists used in asthma treatment.

𝛽3 Adrenergic Receptors Regulation of Lipolysis

• Explains the role of 𝛽3 adrenergic receptors in regulating lipolysis in adipocytes.

𝛽3-Selective Agonist

• Describes the impact of a specific 𝛽3 selective agonist, BRL37344.

GPCRs That Stimulate Phospholipase C Activity: α1-Adrenergic Receptors.

• Discusses how a1-adrenergic receptors influence smooth muscle via phospholipase C activation.

Agonists of Adrenergic Receptors

• Shows agonists for different adrenergic receptors and their corresponding messengers and G proteins.

Effects of epinephrine on blood vessel caliber

• Explains the effects of epinephrine on blood vessel caliber, including the role of different adrenergic receptors in different conditions.

Effect of Catecholamines on Vascular Smooth Muscle

• Describes how epinephrine concentration dictates whether it causes vasoconstriction or vasodilation.

α1 Receptor Agonists

• Discusses specific alpha-1 receptor agonists and their usage.

Adrenergic Receptors Drug List

• Provides a summary list of adrenergic receptor-related drugs.