G Protein‑Coupled Receptor (GPCR) Signaling
Concept Name
GPCR Signaling
Genetic Loci
GNAS (20q13.3) encodes Gsα – activating mutations cause McCune‑Albright syndrome. ADRB2 (5q31‑q32) encodes β2‑adrenergic receptor – polymorphisms affect asthma response.
Intracellular Cascade
Ligand binding → GPCR conformational change → Gα subunit exchanges GDP for GTP → dissociation of Gα‑GTP from Gβγ. Gαs activates adenylyl cyclase (cAMP↑), Gαq activates phospholipase C (IP3/DAG↑), Gαi inhibits adenylyl cyclase. Signaling terminated by RGS proteins (GAP activity) and receptor desensitization (GRK/β‑arrestin).
Required Cofactors
Mg²⁺ is required for GDP/GTP exchange. GTP is essential for Gα activation.
Histology Stains
No specific histological stains; receptor localization is studied by autoradiography or immunohistochemistry with receptor‑specific antibodies.
EM Findings
GPCRs are not visible at EM resolution; however, immunogold labeling can localize receptors to specific membrane domains.
Knockout Phenotype
Knockout of GNAS is embryonic lethal. Tissue‑specific knockout of Gsα in osteoblasts causes severe osteoporosis due to impaired bone formation.
Specific Toxins
Cholera toxin ADP‑ribosylates Gsα, locking it in the active state (irreversible cAMP production). Pertussis toxin ADP‑ribosylates Gαi, preventing inhibition of adenylyl cyclase.