Junctional adhesion molecules (JAMs): more molecules with dual functions?
Junctional adhesion molecules (JAMs) are members of an immunoglobulin subfamily expressed by leukocytes and platelets as well as by epithelial and endothelial cells, in which they localize to cell-cell contacts and are specifically enriched at tight junctions. The recent identification of extracellular ligands and intracellular binding proteins for JAMs suggests two functions for JAMs. JAMs associate through their extracellular domains with the leukocyte beta2 integrins LFA-1 and Mac-1 as well as with the beta1 integrin alpha4beta1. All three integrins are involved in the regulation of leukocyte-endothelial cell interactions. Through their cytoplasmic domains, JAMs directly associate with various tight junction-associated proteins including ZO-1, AF-6, MUPP1 and the cell polarity protein PAR-3. PAR-3 is part of a ternary protein complex that contains PAR-3, atypical protein kinase C and PAR-6. This complex is highly conserved through evolution and is involved in the regulation of cell polarity in organisms from Caenorhabditis elegans and Drosophila to vertebrates. These findings point to dual functions for JAMs: they appear to regulate both leukocyte/platelet/endothelial cell interactions in the immune system and tight junction formation in epithelial and endothelial cells during the acquisition of cell polarity.
Ebnet
Klaus
K
Institute of Cell Biology, ZMBE, University of Münster, 48149 Münster, Germany.
Suzuki
Atsushi
A
Ohno
Shigeo
S
Vestweber
Dietmar
D
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D062726:Junctional Adhesion Molecules; D016547:Kinesins / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008565:Membrane Proteins; D008958:Models, Molecular; D009218:Myosins / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D016023:Integrins; D062726:Junctional Adhesion Molecules; C111442:MPDZ protein, human; D008565:Membrane Proteins; C114255:PAR 3 protein, Trypanosoma cruzi; D015800:Protozoan Proteins; C490658:afd-1 protein, C elegans; C092747:cno protein, Drosophila; D011493:Protein Kinase C; D009218:Myosins; D016547:Kinesins