Neurobiology Quiz on Antibodies and Receptors

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Questions and Answers

What is the mechanism by which antibodies in Myasthenia gravis affect neuromuscular function?

They block the release of acetylcholine.

They enhance the effect of acetylcholine.

They inhibit the nicotinic acetylcholine receptors. (correct)

They activate the nicotinic acetylcholine receptors.

Which type of receptor mutation is associated with epilepsy?

Mutations in ligand-gated ion channels. (correct)

Mutations in tyrosine kinase receptors.

Mutations in voltage-gated calcium channels.

Mutations in growth factor receptors.

What is the role of Na+ channels during depolarization?

They only allow K+ ions to pass through.

They inactivate rapidly to stop K+ efflux.

They open to allow a large influx of Na+ ions. (correct)

They remain closed to prevent Na+ influx.

What causes hyperpolarization in a neuron?

The efflux of K+ ions from the cell. Signup and view all the answers

Which condition is associated with antibodies activating the thyroid-stimulating hormone receptor?

Graves’ disease. Signup and view all the answers

What is the role of PI3K in cellular functions?

Decreases apoptosis and increases cell survival Signup and view all the answers

Which process occurs after the binding of a ligand to a receptor in the PI3K pathway?

Phosphorylation of Akt protein Signup and view all the answers

How do ligand-gated ion channels differ from voltage-gated ion channels?

They require direct binding of exogenous or endogenous ligands. Signup and view all the answers

Which of the following is directly activated by binding ligands?

Ligand ion channels Signup and view all the answers

What is the end product of PI3K activation in the signaling pathway?

pAkt Signup and view all the answers

What is one of the implications of the PI3K/pAkt pathway in cancer?

It is associated with enhanced tumor progression. Signup and view all the answers

Which of the following is an example of a ligand-gated ion channel?

GABAA receptors Signup and view all the answers

What effect does hyperpolarization have on neurons?

Decreases the likelihood of action potential generation Signup and view all the answers

What is the function of the Grb2 protein in the Ras/MAPKs pathway?

It binds to phosphorylated tyrosine to facilitate Ras activation. Signup and view all the answers

Which statement correctly describes the Jak/Stat signaling pathway?

Cytokine binding causes dimerization and autophosphorylation of the receptor. Signup and view all the answers

What role does IκB play in the NFκB pathway?

It binds to NFκB and prevents its activation. Signup and view all the answers

What is the outcome of the activation of the Ras protein in the Ras/MAPKs pathway?

Activation of transcription factors that promote cellular growth. Signup and view all the answers

Which pathway is affected by the inhibition of NFκB signaling?

Inflammatory and autoimmune pathways. Signup and view all the answers

What triggers the activation of the PI3K/Akt pathway?

Binding of phosphatidylinositol to receptor tyrosine kinases (TKRs). Signup and view all the answers

How do Stat proteins contribute to the immune response according to the Jak/Stat pathway?

They migrate to the nucleus to activate gene expression. Signup and view all the answers

What is the significance of Imatinib in cancer treatment?

It targets specific tyrosine kinases involved in leukemia. Signup and view all the answers

What triggers the release of Ca²⁺ from the sarcoplasmic reticulum (SR) in muscle cells?

Opening of Na+ channels Signup and view all the answers

What is the primary function of secondary messengers like cAMP in signal transduction?

Phosphorylation of intracellular targets Signup and view all the answers

What effect does an increase in intracellular Ca²⁺ have on K+ and Cl- channels?

Opens K+ and Cl- channels Signup and view all the answers

What distinguishes Class I nuclear receptors from Class II nuclear receptors?

Class I receptors are found in the cytoplasm Signup and view all the answers

Which of the following receptors is associated with lipid-soluble drugs?

Nuclear receptors Signup and view all the answers

Which of the following statements about β-adrenoceptor agonists is true?

They indirectly affect voltage Ca²⁺ channels Signup and view all the answers

What is the effect of ATP on ATP-dependent K+ channels?

ATP closes K+ channels Signup and view all the answers

What is a common outcome of receptor malformation in relation to health?

Direct links to various diseases Signup and view all the answers

What type of kinase receptor contains a tyrosine kinase residue in its intracellular region?

Tyrosine kinase receptors Signup and view all the answers

Which of the following functions is NOT associated with tyrosine kinases?

Receptor internalization Signup and view all the answers

What activates cytokine receptors?

Cytokines Signup and view all the answers

What is the role of phosphatases in relation to kinase activity?

They dephosphorylate proteins, thereby regulating kinase activity. Signup and view all the answers

In the Ras/MAPKs signaling pathway, what is the first step following ligand binding to a tyrosine kinase receptor?

Dimerization of the receptor Signup and view all the answers

Study Notes

Basic Pharmacology

Basic Pharmacology is a course topic.
Dr. Mamdouh Oraby is the instructor.

2- Kinase-linked pathways

Kinase receptors are a large family of membrane receptors.
These receptors are composed of a large extracellular ligand-binding domain (N-terminal) and an intracellular domain with diverse functions (C-terminal).
Tyrosine kinases have diverse functions, including cell growth and differentiation, cell division, inflammation, tissue repair, apoptosis, and immune response.

Kinase-linked pathways

Tyrosine Kinase Receptors (TKRs):
- Intracellular region contains a tyrosine kinase residue.
- Examples include epidermal growth factor (EGF) receptors and insulin receptors.
Serine/Threonine Kinase Receptors:
- Phosphorylates serine or threonine residues rather than tyrosine.

Cytokine receptors

Activated by cytokines.
Cytokines regulate immune and inflammatory responses, tissue repair, and regeneration.
Intracellular domains of cytokine receptors are tyrosine kinases that activate other kinases, such as Janus kinase (Jak).
Examples include interferons, interleukins, and tumor necrosis factor-alpha (TNF-α).

Kinase-linked pathways - Protein phosphorylation

Kinases are important for activating enzymes, ion channels, and receptors in cellular processes.
They catalyze the transfer of phosphate groups from high-energy phosphate donors (e.g., ATP) to a substrate (protein).
Dephosphorylation is controlled by phosphatases.

Signal transduction of tyrosine kinase (Ras/MAPKs pathway)

Binding a ligand activates a tyrosine kinase.
Dimerization of the receptor occurs, leading to auto-phosphorylation of tyrosine residues.
Autophosphorylation acts as a binding site for SH2-containing proteins (e.g., Grb2).

Signal transduction of tyrosine kinase receptors (TKRS)

Ras/MAPK pathway:
- Phosphorylation of tyrosine residues through SH2 proteins (e.g., Grb2).
- Activation of Ras protein (GTPase-protein).
- Activation of MAPKs (Mitogen-Activated Protein Kinases) by phosphorylation.
- Activation of transcription factors, subsequently entering the nucleus and binding to DNA to regulate gene transcription.
- Cellular growth is a key signaling output.

Importance of tyrosine kinase inhibitors in cancer treatment (Imatinib)

Imatinib is an anticancer drug.
It inhibits specific tyrosine kinase receptors (e.g., those involved in leukemia pathogenesis).

Signal transduction of cytokine receptors (Jak/Stat pathway)

Binding of cytokines to cytokine receptors.
Cytokine receptor dimerization followed by autophosphorylation.
Binding and phosphorylation of Jak proteins (cytosolic tyrosine kinases).
Phosphorylation of SH2 domains of Stat proteins (transcription factors).
Stat proteins migrate to nucleus to activate gene expression.

Stat proteins

Control the synthesis and release of inflammatory mediators.
Involved in the cellular responses to injuries and infections, and activate the immune response.

Signal transduction of cytokine receptors (Nuclear factor kappa-B (NFκB) pathway)

NFκB is a transcription factor involved in inflammation and cancer.
NFκB is inhibited by a cytosolic inhibitor (IkB).
Phosphorylation of IkB by IKK (IκB kinase).
Dissociation of NFκB and its activation.
NFκB enters the nucleus to activate various inflammatory genes.

Binding of cytokines to cytokine receptors

Activation of IKK & phosphorylation of IkB.
Dissociation of IkB & activation of NFκB.
NFκB enters the nucleus, activating growth and inflammatory genes.

Inhibition of NF-κB pathway

Plays a vital role in treating inflammatory and autoimmune diseases and cancer.

Other TKRs pathway (PI3K/Akt)

Phosphatidylinositol-3-kinase (PI3K) is a cytosolic tyrosine kinase.
Activated by GPCRs (G-protein-coupled receptors) and TKRs.
PI3K signaling controls cell differentiation, proliferation, apoptosis, and cell survival.

PI3K/Akt pathway

Ligand (growth factor) binding to receptor (GPCRs or TKRs)
Activation through phosphorylation of PI3K.
PIP2 is converted to PIP3.
PIP3 binds to and phosphorylates Akt protein, activating it.
Regulates protein synthesis, cell cycle progression, proliferation, and survival.
Functions to decrease apoptosis.

PI3K/Akt pathway and cancer

Rational drug design uses molecular targets for PI3K/Akt pathway to treat various cancers, including endometrial cancer.

Ligands & Voltage-gated ion channels

These are transmembrane proteins that regulate ion movement.
They control ion movement through the opening and closing of water-filled pores.

Types of ion channels

Ligand-gated ion channels:
- Activated by endogenous or exogenous ligands.
- Examples include glutamate, GABA, and acetylcholine receptors.
Voltage-gated ion channels:
- Activated by changes in membrane potential.
- Examples include Na+, K+, Cl−, and Ca2+ channels.

Direct activation of ion channels (ligand-gated channels)

Binding of ligands (e.g., barbiturates with GABAA receptors) opens channels, causing either hyperpolarization or depolarization.
Examples include GABAA receptor activation with barbiturates, leading to hyperpolarization and inhibition of neuronal transmission (sedation & anesthesia), and acetylcholine binding to nicotinic receptors leading to muscle contraction.

Indirect activation of voltage ion channels

Binding of ligands to GPCRs triggers intracellular signaling cascades.
Production of second messengers (cAMP, DAG, IP3).
Activation of protein kinases (PKA, PKC).
Phosphorylation of voltage channels, either opening or closing them.
Examples include β-adrenoceptor activation, affecting voltage-gated Ca2+ channels, and muscarinic receptor activation, affecting K+ and Ca2+ channels.

Indirect control by intracellular mediators of voltage-gated ion channels

Ex 1: intracellular Ca2+
Ex 2: Nucleotides such as ATP & GTP, opening K+ or Cl− channels.

Signal transduction of nuclear (DNA) receptors

Receptors for lipid-soluble drugs, hormones, and vitamins.
Includes steroid hormones (e.g., glucocorticoids, estrogens).
Structure:
- C-terminal binds to the ligand.
- DNA-binding domain (zinc fingers) binds to a site on DNA.
- N-terminal binds to other transcriptional factors.
Classification (Class I):
- Receptors found in the cytoplasm.
- Ligand binding to receptor → translocation to the nucleus and binding to specific DNA sequences → gene transcription (e.g., steroid receptors).
Classification (Class II):
- Receptors found in the nucleus.
- Receptor-ligand complex binds to specific DNA binding sites → gene transcription (e.g., peroxisome proliferator-activated receptor (PPAR), thyroid hormone receptors, retinoid X receptors).

Receptor-associated diseases

Antibodies (Abs) directed against receptors:
- Myasthenia gravis: Abs inhibit acetylcholine receptors.
- Graves' disease: Abs activate thyroid-stimulating hormone receptors.
Mutations in genes encoding receptors:
- Mutations in ligand-gated ion channels (e.g., GABAA, nicotinic receptors) can cause epilepsy.
- Mutations in GPCRs and kinases can cause various diseases.
- Mutations in growth factor receptors can lead to cancer development.

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Description

Test your knowledge about the mechanisms of antibodies in Myasthenia gravis, receptor mutations related to epilepsy, and the role of ion channels in neuron function. Explore concepts of depolarization, hyperpolarization, and hormonal interactions in this neurobiology quiz.