SynCAM, a synaptic adhesion molecule that drives synapse assembly.
Synapses, the junctions between nerve cells through which they communicate, are formed by the coordinated assembly and tight attachment of pre- and postsynaptic specializations. We now show that SynCAM is a brain-specific, immunoglobulin domain-containing protein that binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion molecule at the synapse. Expression of the isolated cytoplasmic tail of SynCAM in neurons inhibited synapse assembly. Conversely, expression of full-length SynCAM in nonneuronal cells induced synapse formation by cocultured hippocampal neurons with normal release properties. Glutamatergic synaptic transmission was reconstituted in these nonneuronal cells by coexpressing glutamate receptors with SynCAM, which suggests that a single type of adhesion molecule and glutamate receptor are sufficient for a functional postsynaptic response.
Biederer
Thomas
T
Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Thomas.Biederer@UTSouthwestern.edu
Sara
Yildirim
Y
Mozhayeva
Marina
M
Atasoy
Deniz
D
Liu
Xinran
X
Kavalali
Ege T
ET
Südhof
Thomas C
TC
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology*; D001923:Brain Chemistry; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D005089:Exocytosis; D006801:Humans; D007136:Immunoglobulins; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology; D016548:Prosencephalon / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection; D025521:Tumor Suppressor Proteins
C465040:Cadm1 protein, rat; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C104722:glutamate receptor ionotropic, AMPA 2