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The Journal of Neuroscience, November 14, 2007, 27(46):12516-12530; doi:10.1523/JNEUROSCI.2739-07.2007
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Cellular/Molecular
SynCAMs Organize Synapses through Heterophilic Adhesion
Adam I. Fogel,1
Michael R. Akins,1 *
Alexander J. Krupp,2 *
Massimiliano Stagi,1 *
Valentin Stein,2 and
Thomas Biederer1
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, and 2Max Planck Institute of Neurobiology, 82152 Martinsried, Germany
Correspondence should be addressed to Thomas Biederer, Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520. Email: thomas.biederer{at}yale.edu
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.
Key words: SynCAM; CADM; synapse; synaptic adhesion; synaptogenesis; synaptic transmission
Received June 16, 2007;
revised Aug. 27, 2007;
accepted Sept. 25, 2007.
Correspondence should be addressed to Thomas Biederer, Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520. Email: thomas.biederer{at}yale.edu
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