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Interaction of AQP2 and integrin b1 is important for the maintenance of epithelial structure and function
Author(s) -
Lu hua jenny,
rice william,
li wei,
chen ying
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.809.10
Subject(s) - aquaporin 2 , microbiology and biotechnology , integrin , integrin linked kinase , internalization , apical membrane , chemistry , endocytosis , biology , cell , water channel , phosphorylation , protein kinase a , biochemistry , membrane , mechanical engineering , cyclin dependent kinase 2 , engineering , inlet
Kidney tubular epithelium contributes critically to the regulation and maintenance of electrolyte, acid and base, and water balance in the body. Aquaporin 2 is the water channel expressed in the principal cells of the collecting ducts (CDs) of the kidneys. It regulates water re‐absorption in the CDs in response to the antidiuretic hormone, vasopressin (VP). Extensive studies from our group and others have revealed a complex regulatory network of AQP2 trafficking inside cells. More recently, study from our lab has shown that AQP2 is not only a water channel but also an integrin binding membrane protein. Through interacting with integrin b1, AQP2 modulates the internalization and trafficking of integrin b1, facilitates its turnover at the focal adhesions, and results in increased cell migration. Disrupting the interaction between AQP2 and integrin b1 by mutating the RGD motif led to reduced endocytosis, cell surface retention of integrin b1, defective cell migration and tubulogenesis. In addition, we show here that interaction of AQP2 and integrin b1 is also important for maintaining a polarized, subcellular distribution of integrin b1 in epithelium. Uncoupling of AQP2 and integrin interaction (through mutating the RGD‐integrin binding motif of AQP2, or using AQP2 null animals) leads to redistribution of integrin b1 from the basal membrane domain to the lateral membrane domain in polarized cell culture and in AQP2 knock out animals. This redistribution of integrin b1 is associated with aberrant expression of the serine/threonine kinase Akt in cells. In summary, our data suggest that besides transporting water, the water channel AQP2 plays a novel role and contributes importantly to the structural and functional integrity of the renal tubular epithelium through interacting with integrin b1.