aquaporin2

Aquaporin-2 (AQP2) is a membrane water channel protein belonging to the aquaporin superfamily. In humans, AQP2 is predominantly expressed in principal cells of the renal collecting ducts and assembles as tetramers to form water-permeable pores.

AQP2 mediates transcellular water reabsorption, a key component of the antidiuretic response. Vasopressin (antidiuretic hormone) binds V2 receptors on the basolateral membrane, activating adenylyl cyclase and raising cAMP. cAMP-dependent protein kinase A phosphorylates AQP2, triggering translocation of AQP2-containing vesicles to the apical membrane, increasing apical water permeability and water reabsorption. Upon reduced vasopressin, AQP2 is endocytosed, decreasing water permeability. Longer-term control also involves regulation of AQP2 gene transcription and protein abundance.

Structure and localization: Each AQP2 monomer spans the membrane six times; four monomers form a tetramer that constitutes the functional water pore. AQP2 is glycosylated and trafficked from intracellular storage vesicles to the apical surface in response to vasopressin.

Clinical relevance: Mutations in AQP2 can cause nephrogenic diabetes insipidus (NDI), a condition characterized by impaired kidney concentrating ability and polyuria. Lithium therapy and certain conditions can disrupt AQP2 trafficking, leading to nephrogenic DI. Treatments address water loss and may include thiazide diuretics, NSAIDs, and dietary adjustments.