The vasopressin (ADH) V2 receptor on principal cells of the collecting duct signals via Gs → adenylyl cyclase → cAMP → PKA. PKA phosphorylates AQP2 at Ser256 to promote vesicle insertion. Which additional action of phosphorylated AQP2 also reduces its degradation and contributes to sustained antidiuresis?
- A Phospho-AQP2 is internalized by clathrin-coated pits and recycled to the basolateral membrane
- B Phospho-AQP2 at Ser256 prevents ubiquitination and lysosomal degradation, stabilizing the apical membrane pool ✓
- C Phospho-AQP2 opens adjacent AQP4 channels in the basolateral membrane to increase water efflux
- D Phospho-AQP2 activates ENaC channels to increase Na⁺ reabsorption and generate osmotic gradient
Correct answer: B. Phospho-AQP2 at Ser256 prevents ubiquitination and lysosomal degradation, stabilizing the apical membrane pool
Explanation
PKA-mediated phosphorylation of AQP2 at Ser256 serves a dual role: it triggers translocation of AQP2-bearing vesicles to the apical membrane AND prevents AQP2 ubiquitination (at Lys270), which would otherwise target the protein for proteasomal/lysosomal degradation. This stabilizes the apical membrane pool and sustains water permeability. Lithium toxicity and nephrogenic DI impair this signaling cascade; V2 receptor mutations cause X-linked nephrogenic DI.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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