Submitted on May 22, 2008
Revised on December 9, 2008
Accepted on December 24, 2008
Nectin proteins are expressed at early stages of nephrogenesis and play a role in renal epithelial cell morphogenesis
Paul R Brakeman1*, Kathleen D Liu1, Kazuya Shimizu, Yoshimi Takai2, and Keith E. Mostov
1 University of California, San Francisco
2 Osaka University
* To whom correspondence should be addressed. E-mail: brakemanp{at}peds.ucsf.edu.
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 concurrent with the transition of mesenchymal cells into epithelial cells. We have defined the role of nectin during epithelial cell morphogenesis by studying nectin in 3-dimensional culture of Madin-Darby Canine Kidney (MDCK) cells. In 3-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 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 anti-apoptotic signal and promoting the formation of TJs and cell polarity.
