title: Aquaporin 2 promotes cell migration and epithelial morphogenesis.
abstract: The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin β1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin β1 by mutating the RGD motif led to reduced endocytosis, retention of integrin β1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin β1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney.
authors.affiliation: Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Rice
authors.forename: Zhizhan
authors.initials: Z
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Huang
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Alfred
authors.initials: A
authors.lastname: Van Hoek
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiong
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
authors.forename: Jim C
authors.initials: JC
authors.lastname: Norman
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fenton
authors.forename: Dennis
authors.initials: D
authors.lastname: Brown
authors.forename: Hua A Jenny
authors.initials: HA
authors.lastname: Lu
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004285:Dogs; D004705:Endocytosis / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000502:physiology; D007668:Kidney / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000235:genetics / Q000502:physiology; D013552:Swine; D014162:Transfection
chemical_list: D051399:Aquaporin 2; D019012:Integrin beta1; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid