Expression of a soluble isoform of cell adhesion molecule 1 in the brain and its involvement in directional neurite outgrowth

Am J Pathol. 2009 Jun;174(6):2278-89. doi: 10.2353/ajpath.2009.080743. Epub 2009 May 12.


Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed on superior cervical ganglion neurites and mediates cell-cell adhesion by trans-homophilic binding. In addition to the membrane-bound form, we have previously shown that a soluble form (sCADM1) generated by alternative splicing possesses a stop codon immediately downstream of the immunoglobulin-like domain. Here, we demonstrate the presence of sCADM1 in vivo and its possible role in neurite extension. sCADM1 appears to be a stromal protein because extracellular-restricted, but not intracellular-restricted, anti-CADM1 antibody stained stromal protein-rich extract from mouse brains. Murine plasmacytoma cells, P3U1, were modified to secrete sCADM1 fused with either immunoglobulin (Ig)G Fc portion (sCADM1-Fc) or its deletion form that lacks the immunoglobulin-like domain (DeltasCADM1-Fc). When P3U1 derivatives expressing sCADM1-Fc or DeltasCADM1-Fc were implanted into collagen gels, Fc-fused proteins were present more abundantly around the cells. Superior cervical ganglion neurons, parental P3U1, and either derivative were implanted into collagen gels separately, and co-cultured for 4 days. Bodian staining of the gel sections revealed that most superior cervical ganglion neurites turned toward the source of sCADM1-Fc, but not DeltasCADM1-Fc. Furthermore, immunofluorescence signals for sCADM1-Fc and membrane-bound CADM1 were co-localized on the neurite surface. These results show that sCADM1 appears to be involved in directional neurite extension by serving as an anchor to which membrane-bound CADM1 on the neurites can bind.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Coculture Techniques
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Immunoprecipitation
  • In Situ Nick-End Labeling
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Neurites / metabolism*
  • Protein Isoforms / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction


  • Protein Isoforms
  • Intercellular Adhesion Molecule-1