The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM).
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.
Ebnet
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Institute of Cell Biology, ZMBE, University of Muenster, D-48149 Muenster, Germany.
Suzuki
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A
Horikoshi
Y
Y
Hirose
T
T
Meyer Zu Brickwedde
M K
MK
Ohno
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S
Vestweber
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D
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005799:Genes, Dominant; D015801:Helminth Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D062726:Junctional Adhesion Molecules; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; D062726:Junctional Adhesion Molecules; C115084:Pard3 protein, mouse; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases