Major Transmembrane Signalling Systems

Overview

There are four primary transmembrane signalling systems:

• Ligand-gated ion channels
• G-protein coupled receptors
• Enzyme-linked receptors
• Intracellular receptors

1. Ligand-Gated Ion Channels

• Ligands: Typically neurotransmitters such as acetylcholine.
• Mechanism:
  • Ligands cross the synaptic cleft at the neuromuscular junction.
  • Bind to nicotinic receptors linked to ion channels.
  • Induces conformational changes, opening ion channels.
  • Allows influx of ions (e.g., sodium ions), modulating cellular action potential.

2. G-Protein Coupled Receptors

• Mechanism:
  • Ligand binding induces conformational change in the receptor.
  • Activates the G protein's alpha subunit.
  • GDP dissociates; GTP binds to the alpha subunit.
  • Alpha subunit dissociates from beta and gamma subunits, forming a beta-gamma dimer.
  • Both alpha subunit and beta-gamma dimer activate various effector targets:
    • Example: Alpha subunit activates adenylate cyclase and phospholipase C.
    • Leads to a cascade of second messenger reactions and biological responses.

3. Enzyme-Linked Receptors

• Example: Insulin receptors.
• Mechanism:
  • Insulin binds to the extracellular domain of the receptor.
  • Stimulates conformational change, activating tyrosine kinase enzyme (part of the intracellular domain).
  • Tyrosine kinase phosphorylates insulin receptor substrate (IRS).
  • IRS stimulates a cascade of various biological responses.
• Key Difference: Tyrosine kinase is an intrinsic part of the receptor, unlike in G-protein coupled receptors.

4. Intracellular Receptors

• Ligands: Lipophilic molecules such as steroid hormones.
• Mechanism:
  • Molecules pass through the cell membrane.
  • Bind to and activate intracellular receptors.
  • Activated receptors regulate gene expression.

Credits

• Narrated by Zainab Hamad, a medical student at King's College London.