Aquaporin 2 promotes cell migration and epithelial morphogenesis

Chen, Y. et al. (2012) Aquaporin 2 promotes cell migration and epithelial morphogenesis. Journal of the American Society of Nephrology, 23(9), pp. 1506-1517. (doi:10.1681/ASN.2012010079)

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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 beta 1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin beta 1 by mutating the RGD motif led to reduced endocytosis, retention of integrin beta 1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin beta 1 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Norman, Professor James
Authors: Chen, Y., Rice, W., Gu, Z., Li, J., Huang, J., Brenner, M.B., Van Hoek, A., Xiong, J., Gundersen, G.G., Norman, J.C., Hsu, V.W., Fenton, R.A., Brown, D., and Lu, H.A.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of the American Society of Nephrology
ISSN:1046-6673
Published Online:02 August 2012

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