title: Nectin proteins are expressed at early stages of nephrogenesis and play a role in renal epithelial cell morphogenesis.
abstract: 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.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, University of California, Box 0748, San Francisco, California 94143-0748, USA. brakemanp@peds.ucsf.edu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Brakeman
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimizu
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.forename: Keith E
authors.initials: KE
authors.lastname: Mostov
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D016764:Cell Polarity; D054338:Cell Transdifferentiation; D003094:Collagen; D024042:Collagen Type I / Q000502:physiology; D004285:Dogs; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D007797:Laminin; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009024:Morphogenesis; D000075983:Nectins; D062793:Occludin; D011509:Proteoglycans; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D024042:Collagen Type I; D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; D008840:Microfilament Proteins; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D062793:Occludin; C568986:Ocln protein, mouse; C115084:Pard3 protein, mouse; D011509:Proteoglycans; C108835:afadin; C059485:matrigel; D003094:Collagen