A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2.
Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice. Forskolin and [desamino-Cys(1), D-Arg(8)]-vasopressin (DDAVP)-induced AQP2 exocytosis was impaired in VAMP8-null collecting duct cells. VAMP8 was revealed to colocalize with AQP2 on intracellular vesicles and to interact with the plasma membrane t-SNARE proteins syntaxin4 and syntaxin3, suggesting that VAMP8 mediates the regulated fusion of AQP2-positive vesicles with the plasma membrane.
Wang
Cheng-Chun
CC
Institute of Molecular and Cell Biology, 61 Biopolis Dr., Singapore 138673, Singapore.
Ng
Chee Peng
CP
Shi
Hong
H
Liew
Hwee Chien
HC
Guo
Ke
K
Zeng
Qi
Q
Hong
Wanjin
W
D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis*; D002478:Cells, Cultured; D005089:Exocytosis; D006869:Hydronephrosis / Q000235:genetics / Q000503:physiopathology; D042541:Intracellular Space / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C491831:Vamp8 protein, mouse