Molecular mechanisms and drug development in aquaporin water channel diseases: molecular mechanism of water channel aquaporin-2 trafficking.
Targeted positioning of water channel aquaporin-2 (AQP2) strictly regulates body water homeostasis. Trafficking of AQP2 to the apical membrane is critical for the reabsorption of water in renal collecting ducts. Besides the cAMP-mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other signaling cascades also induce this sorting. Recently, AQP2-binding proteins that directly regulate this trafficking have been uncovered: SPA-1, a GTPase-activating protein (GAP) for Rap1, and cytoskeletal protein actin. This review summarizes recent advances related to the trafficking mechanism of AQP2 and its defect causing nephrogenic diabetes insipidus (NDI).
Noda
Yumi
Y
Department of Nephrology, Graduate School, Tokyo Medical and Dental University, Japan. ynodmed2@tmd.ac.jp
Sasaki
Sei
S
D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D009154:Mutation; D021381:Protein Transport / Q000502:physiology
C496023:AQP2 protein, human; D051399:Aquaporin 2; D020346:Aquaporins