Aquaporin 2 promotes cell migration and epithelial morphogenesis

Ying Chen, William Rice, Zhizhan Gu, Jian Li, Jianmin Huang, Michael B. Brenner, Alfred Van Hoek, Jianping Xiong, Gregg G. Gundersen, Jim C. Norman, Victor W. Hsu, Robert A. Fenton, Dennis Brown, Hua A.Jenny Lu

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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 b1 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.

Original languageEnglish (US)
Pages (from-to)1506-1517
Number of pages12
JournalJournal of the American Society of Nephrology
Volume23
Issue number9
DOIs
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Nephrology

Fingerprint

Dive into the research topics of 'Aquaporin 2 promotes cell migration and epithelial morphogenesis'. Together they form a unique fingerprint.

Cite this