title: Synaptic scaffolding molecule (S-SCAM) membrane-associated guanylate kinase with inverted organization (MAGI)-2 is associated with cell adhesion molecules at inhibitory synapses in rat hippocampal neurons.
abstract: Synaptic scaffolding molecule (S-SCAM) is a synaptic protein, which harbors five or six PSD-95/Discs large/ZO-1 (PDZ), a guanylate kinase and two WW domains. It interacts with NMDA receptor subunits, neuroligin and beta-catenin, and is involved in the accumulation of neuroligin at excitatory synapses. In this study, we have demonstrated S-SCAM is localized at inhibitory synapses in rat primary cultured hippocampal neurons. We have identified beta-dystroglycan (beta-DG) as a binding partner for S-SCAM at inhibitory synapses. WW domains of S-SCAM bind to three sequences of beta-DG. We have also revealed that S-SCAM can interact with neuroligin 2, which is known to be exclusively localized at inhibitory synapses. The WW domains and the second PDZ domain of S-SCAM are involved in the interaction with neuroligin 2. Beta-DG, neuroligin 2 and S-SCAM form a tripartite complex in vitro. Neuroligin 2 is detected in the immunoprecipitates by anti-beta-DG antibody from rat brain. S-SCAM, beta-DG and neuroligin 2 are partially co-localized in rat hippocampal neurons. These data suggest that S-SCAM is associated with beta-DG and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin-neuroligin complex.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sumita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.forename: Junko
authors.initials: J
authors.lastname: Iida
authors.forename: Akira
authors.initials: A
authors.lastname: Kawata
authors.forename: Mamiko
authors.initials: M
authors.lastname: Hamano
authors.forename: Susumu
authors.initials: S
authors.lastname: Hirabayashi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Ohno
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D017434:Protein Structure, Tertiary; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D020798:Two-Hybrid System Techniques / Q000401:mortality
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491276:Dlgap1 protein, rat; C114103:Magi2 protein, rat; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D051528:Guanylate Kinases