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Am J Physiol Renal Physiol 296: F564-F574, 2009. First published December 30, 2008; doi:10.1152/ajprenal.90328.2008
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Nectin proteins are expressed at early stages of nephrogenesis and play a role in renal epithelial cell morphogenesis

Paul R. Brakeman,1 Kathleen D. Liu,2 Kazuya Shimizu,3 Yoshimi Takai,3,4 and Keith E. Mostov5

1Division of Pediatric Nephrology, Departments of Pediatrics, 2Medicine, and 5Anatomy, University of California, San Francisco; California; 3Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine, Osaka; and 4Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

Submitted 22 May 2008 ; accepted in final form 24 December 2008

Development of the nephron requires conversion of the metanephric mesenchyme into tubular epithelial structures with specifically organized intercellular junctions. The nectin proteins are a family of transmembrane proteins that dimerize to form intercellular junctional complexes between epithelial cells. In this study, we demonstrate that nectin junctions appear during the earliest stages of epithelial cell morphogenesis in the murine nephron concurrently with the transition of mesenchymal cells into epithelial cells. We have defined the role of nectin during epithelial cell morphogenesis by studying nectin in a three-dimensional culture of Madin-Darby canine kidney (MDCK) cells. In a three-dimensional culture of MDCK cells grown in purified type 1 collagen, expression of a dominant negative form of nectin causes disruption of the formation of cell polarity and disruption of tight junction (TJ) formation, as measured by zonula occludens-1 (ZO-1) localization. In MDCK cells cultured in Matrigel, exogenous expression of nectin-1 causes disruption of normal epithelial cell cyst formation and decreased apoptosis. These data demonstrate that nectins play an important role in normal epithelial cell morphogenesis and may play a role in mesenchymal-to-epithelial transition during nephrogenesis by providing an antiapoptotic signal and promoting the formation of TJs and cell polarity.

cell polarity; three-dimensional cell culture; PAR-3


Address for reprint requests and other correspondence: P. R. Brakeman, Dept. of Pediatrics, Univ. of California, Box 0748, San Francisco, CA 94143-0748 (e-mail: brakemanp{at}peds.ucsf.edu)






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