Interaction of synaptic scaffolding molecule and Beta -catenin.
Synaptic scaffolding molecule (S-SCAM) is a synaptic membrane-associated guanylate kinase with inverted domain organization (MAGI) that interacts with NMDA receptor subunits and neuroligin. In epithelial cells, the non-neuronal isoform of S-SCAM (MAGI-1) is localized at tight or adherens junctions. Recent studies have revealed that the polarized targeting of MAGI-1 to the lateral membrane is mediated by its C-terminal region and that MAGI-1 interacts with beta-catenin in epithelial cells. In this article, we report that S-SCAM interacts with beta-catenin in neurons. beta-Catenin is coimmunoprecipitated with S-SCAM from rat brain. Both S-SCAM and beta-catenin are localized at synapses and are partially colocalized. The C-terminal region of S-SCAM binds to the C-terminal region of beta-catenin. We have tested how the interaction between S-SCAM and beta-catenin plays a role in the synaptic targeting of S-SCAM and beta-catenin. S-SCAM is targeted to synapses via the C-terminal postsynaptic density-95/Dlg-A/ZO-1 (PDZ) domain. beta-Catenin is targeted to synapses with armadillo repeats. The overexpressed C-terminal region of beta-catenin blocks the synaptic targeting of S-SCAM. The overexpressed C-terminal region of S-SCAM is partially targeted to synapses and forms a small number of clusters. In the presence of overexpressed beta-catenin, the C-terminal region of S-SCAM forms more clusters at synapses. These data suggest that the synaptic targeting of S-SCAM is mediated by the interaction with beta-catenin.
Nishimura
Wataru
W
Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Yao
Ikuko
I
Iida
Junko
J
Tanaka
Noriaki
N
Hata
Yutaka
Y
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D015534:Trans-Activators; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; C114103:Magi2 protein, rat; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases