Unbound MEDLINE

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.

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  • Publisher Full Text

    • Authors

    Chen Y, Rice W, Gu Z, Li J, Huang J, Brenner MB, Van Hoek A, Xiong J, Gundersen GG, Norman JC, Hsu VW, Fenton RA, Brown D, Lu HA

    Institution

    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.

    Source

    Journal of the American Society of Nephrology : JASN 23:9 2012 Sep pg 1506-17

    MeSH

    Animals
    Antigens, CD29
    Aquaporin 2
    Cell Line
    Cell Membrane Permeability
    Cell Movement
    Dogs
    Endocytosis
    Epithelial Cells
    Kidney
    Mice
    Mice, Knockout
    Models, Animal
    Morphogenesis
    Mutation
    Oligopeptides
    Swine
    Transfection

    Pub Type(s)

    In Vitro
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22859853