Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion

Mol Biol Cell. 2005 Oct;16(10):4992-5003. doi: 10.1091/mbc.e05-04-0310. Epub 2005 Aug 10.

Abstract

The junctional adhesion molecules (JAMs) have been recently described as interendothelial junctional molecules and as integrin ligands. Here we show that JAM-B and JAM-C undergo heterophilic interaction in cell-cell contacts and that JAM-C is recruited and stabilized in junctional complexes by JAM-B. In addition, soluble JAM-B dissociates soluble JAM-C homodimers to form JAM-B/JAM-C heterodimers. This suggests that the affinity of JAM-C monomers to form dimers is higher for JAM-B than for JAM-C. Using antibodies against JAM-C, the formation of JAM-B/JAM-C heterodimers can be abolished. This liberates JAM-C from its vascular binding partner JAM-B and makes it available on the apical side of vessels for interaction with its leukocyte counter-receptor alpha(M)beta2 integrin. We demonstrate that the modulation of JAM-C localization in junctional complexes is a new regulatory mechanism for alpha(M)beta2-dependent adhesion of leukocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Coculture Techniques
  • Cricetinae
  • Cricetulus
  • Endothelium / physiology
  • Endothelium / ultrastructure
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Intercellular Junctions / physiology*
  • Intercellular Junctions / ultrastructure
  • Leukocytes / physiology*
  • Leukocytes / ultrastructure
  • Macrophage-1 Antigen / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Immunoelectron
  • Oligopeptides
  • Peptides / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Cell Adhesion Molecules
  • Immunoglobulins
  • Macrophage-1 Antigen
  • Oligopeptides
  • Peptides
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • FLAG peptide