SynCAMs organize synapses through heterophilic adhesion

J Neurosci. 2007 Nov 14;27(46):12516-30. doi: 10.1523/JNEUROSCI.2739-07.2007.


Synapses are asymmetric cell junctions with precisely juxtaposed presynaptic and postsynaptic sides. Transsynaptic adhesion complexes are thought to organize developing synapses. The molecular composition of these complexes, however, remains incompletely understood, precluding us from understanding how adhesion across the synaptic cleft guides synapse development. Here, we define two immunoglobulin superfamily members, SynCAM 1 and 2, that are expressed in neurons in the developing brain and localize to excitatory and inhibitory synapses. They function as cell adhesion molecules and assemble with each other across the synaptic cleft into a specific, transsynaptic SynCAM 1/2 complex. Additionally, SynCAM 1 and 2 promote functional synapses as they increase the number of active presynaptic terminals and enhance excitatory neurotransmission. The interaction of SynCAM 1 and 2 is affected by glycosylation, indicating regulation of this adhesion complex by posttranslational modification. The SynCAM 1/2 complex is representative for the highly defined adhesive patterns of this protein family, the four members of which are expressed in neurons in divergent expression profiles. SynCAMs 1, 2, and 3 each can bind themselves, yet preferentially assemble into specific, heterophilic complexes as shown for the synaptic SynCAM 1/2 interaction and a second complex comprising SynCAM 3 and 4. Our results define SynCAM proteins as components of novel heterophilic transsynaptic adhesion complexes that set up asymmetric interactions, with SynCAM proteins contributing to synapse organization and function.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • Cells, Cultured
  • Coculture Techniques
  • Hippocampus / embryology*
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Humans
  • Immunoglobulins
  • Macromolecular Substances / metabolism
  • Mice
  • Neural Pathways / embryology*
  • Neural Pathways / metabolism*
  • Neural Pathways / ultrastructure
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / metabolism*
  • Synaptic Membranes / metabolism
  • Synaptic Membranes / ultrastructure
  • Synaptic Transmission / physiology
  • Tumor Suppressor Proteins / metabolism*


  • Cadm1 protein, rat
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Immunoglobulins
  • Macromolecular Substances
  • Protein Isoforms
  • Tumor Suppressor Proteins