Aquaporin-2 (AQP2) channels are inserted into the principal cell apical membrane in response to ADH. The intracellular signaling cascade involves: ADH → V2 receptor → Gs → adenylyl cyclase → cAMP → PKA → phosphorylation of AQP2 → vesicle fusion. Which specific amino acid residue on AQP2 is phosphorylated by PKA to trigger exocytosis?

• A Threonine-269
• B Serine-126
• C Tyrosine-72
• D Serine-256 ✓

Explanation

PKA phosphorylates AQP2 specifically at Serine-256 in the C-terminal tail, which triggers translocation of AQP2-containing vesicles to the apical membrane via cytoskeletal rearrangement. This is a well-established molecular mechanism relevant to nephrogenic diabetes insipidus (NDI) where V2 receptor mutations prevent this cascade, and lithium toxicity which disrupts intracellular signaling downstream of V2 receptor. AQP3 and AQP4 are constitutively expressed on the basolateral membrane and are not acutely regulated by ADH.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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