Aquaporin-2 protein dynamics within the cell.

PURPOSE OF REVIEW: Aquaporin-2 is an aquaporin water channel protein present at the apical membrane of kidney collecting duct cells and plays a key role in urine concentrating ability. Like other membrane proteins, aquaporin-2 undergoes dynamic processes within the cells: synthesized, targeted to the subapical region, exocytosed to the apical membrane, endocytosed, recycled and finally degraded. The understanding of the molecular and cellular mechanisms of these events is advancing rapidly, and recent new findings characterizing such processes are reviewed.

RECENT FINDINGS: Hypertonicity itself stimulates aquaporin-2 expression through the tonicity-responsive enhancer and its transcription factors. Gene targeted mouse models for human nephrogenic diabetes insipidus show the importance of the C-terminus of aquaporin-2 in apical sorting and provide mechanistic insights. Evidence for the importance of actin cytoskelton in exocytosis of aquaporin-2 to the apical membrane is accumulating. Actin and other proteins bind to aquaporin-2 and make a multiprotein complex. New proteomic analyses indicate the involvement of a large series of proteins in aquaporin-2 dynamics.

SUMMARY: The protein-level understanding of aquaporin-2 dynamics has advanced considerably over the past few years, and continuing studies will open a new way in developing new manoeuvres or drugs to manipulate kidney water homeostasis.