The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)

EMBO J. 2001 Jul 16;20(14):3738-48. doi: 10.1093/emboj/20.14.3738.

Abstract

The establishment and maintenance of cellular polarity are critical for the development of multicellular organisms. PAR (partitioning-defective) proteins were identified in Caenorhabditis elegans as determinants of asymmetric cell division and polarized cell growth. Recently, vertebrate orthologues of two of these proteins, ASIP/PAR-3 and PAR-6, were found to form a signalling complex with the small GTPases Cdc42/Rac1 and with atypical protein kinase C (PKC). Here we show that ASIP/PAR-3 associates with the tight-junction-associated protein junctional adhesion molecule (JAM) in vitro and in vivo. No binding was observed with claudin-1, -4 or -5. In fibroblasts and CHO cells overexpressing JAM, endogenous ASIP is recruited to JAM at sites of cell-cell contact. Over expression of truncated JAM lacking the extracellular part disrupts ASIP/PAR-3 localization at intercellular junctions and delays ASIP/PAR-3 recruitment to newly formed cell junctions. During junction formation, JAM appears early in primordial forms of junctions. Our data suggest that the ASIP/PAR-3-aPKC complex is tethered to tight junctions via its association with JAM, indicating a potential role for JAM in the generation of cell polarity in epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Blotting, Western
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Cycle Proteins
  • Cell Line
  • Cell Polarity*
  • Cytoplasm / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Genes, Dominant
  • Helminth Proteins / metabolism*
  • Immunohistochemistry
  • Junctional Adhesion Molecules
  • Mutation
  • Precipitin Tests
  • Protein Binding
  • Protein Serine-Threonine Kinases
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Helminth Proteins
  • Junctional Adhesion Molecules
  • Pard3 protein, mouse
  • PAR-3 protein, C elegans
  • Protein Serine-Threonine Kinases