Membrane Signaling and Receptors
Core concepts
Cells receive signals through membrane receptors that convert an extracellular ligand into an intracellular response - signal transduction. Know the major receptor classes: G protein-coupled receptors (GPCRs, seven transmembrane helices, activate heterotrimeric G proteins), receptor tyrosine kinases (RTKs, dimerize and autophosphorylate), ion-channel-linked receptors, and ligand-gated nuclear receptors (though these are intracellular). Second messengers (cAMP, IP3, DAG, Ca2+) amplify and spread the signal.
Concepts to name
- Ligand, receptor, transducer, effector, second messenger
- GPCR → G protein → adenylyl cyclase → cAMP → PKA; or PLC → IP3/DAG → Ca2+/PKC
- RTK dimerization, autophosphorylation, docking of signaling proteins
- Amplification, specificity, desensitization
Traps
- Assuming a G protein is always stimulatory - Gs activates adenylyl cyclase, Gi inhibits it.
- Forgetting that RTKs must dimerize before autophosphorylation.
- Confusing first messenger (the ligand) with second messenger (intracellular, e.g., cAMP).
- Overlooking amplification: one ligand can trigger many downstream events.
- Treating receptor binding as irreversible - most signaling is reversible and desensitizes.
Worked example / rule of thumb
Rule: "Ligand outside, cascade inside." Trace the path: epinephrine binds a GPCR → Gs activates adenylyl cyclase → cAMP rises → PKA phosphorylates targets. If asked where amplification occurs, point to the enzymatic steps (one adenylyl cyclase makes many cAMP). If asked about specificity, point to receptor-ligand matching.