Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases

Neurosci Lett. 2008 Oct 17;444(1):16-21. doi: 10.1016/j.neulet.2008.08.023. Epub 2008 Aug 13.


RA175/SynCAM1, a member of immunoglobulin superfamily 4 (Igsf4; recently named Cadm1), is a cell adhesion molecule involved in the formation of a functional synapse. Little is known about the modulation of RA175/SynCAM1-mediated synaptic formation and plasticity. Neurons express two major isoforms containing exons 7-8a-8b-9 and exons 7-8b-9. We found that these isoforms were processed within an 11-amino acid sequence, encoded by exon 8b, near the transmembrane domain. TNF-alpha protease inhibitor-1 (TAPI-1) blocked the processing of RA175/SynCAM1 (exons 7-8a-8b-9). Furthermore, TAPI-1 increased the number of synaptophysin and RA175/SynCAM1 colocalization on the dendrites of neurons. Non-cleaved RA175/SynCAM1 was located at the synapse and membrane-bound, cleaved fragments were detected at the non-synaptic region of dendrites. These results suggest that tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases play a role in synaptic formation to generate specific neuronal connections by processing the excess amount of RA175/SynCAM1 located in the non-synaptic region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Animals
  • COS Cells / drug effects
  • COS Cells / physiology
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cerebral Cortex / cytology
  • Chlorocebus aethiops
  • Dipeptides / pharmacology
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Exons / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hydroxamic Acids / pharmacology
  • Immunoglobulins
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism*
  • Protein Isoforms / metabolism
  • Rats
  • Synaptophysin / metabolism
  • Transfection
  • Tumor Suppressor Proteins / metabolism*


  • Cadm1 protein, rat
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Dipeptides
  • Hydroxamic Acids
  • Immunoglobulins
  • N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide
  • Protein Isoforms
  • Synaptophysin
  • Tumor Suppressor Proteins
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, mouse
  • Adam17 protein, rat