Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin.
S-SCAM has a similar molecular organization to PSD-95. Both of them interact with a cell adhesion molecule, neuroligin. We previously reported that beta-catenin binds S-SCAM and recruits it to synapses. We have here examined using rat primary cultured neurons whether neuroligin recruits S-SCAM to synapses or S-SCAM determines the localization of neuroligin. Overexpressed neuroligin formed larger clusters under co-expression of S-SCAM but not of PSD-95. Overexpressed neuroligin blocked synaptic accumulation of PSD-95 but not of S-SCAM. S-SCAM mutant containing the neuroligin-binding region interfered with synaptic accumulation of neuroligin and PSD-95, whereas the similar mutant of PSD-95 had no effect. Biochemical studies revealed that neuroligin forms a ternary complex with S-SCAM and PSD-95 through manifold interactions. These findings imply that S-SCAM is tethered by beta-catenin to synapses and induces synaptic accumulation of neuroligin, which subsequently recruits PSD-95 to synapses.
Iida
Junko
J
Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Hirabayashi
Susumu
S
Sato
Yuji
Y
Hata
Yutaka
Y
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; C114103:Magi2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D051176:beta Catenin; C093438:neuroligin 1; C033652:postsynaptic density proteins; D051528:Guanylate Kinases