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The Journal of Neuroscience, February 1, 2002, 22(3):757-765

Interaction of Synaptic Scaffolding Molecule and beta -Catenin

Wataru Nishimura1, 2, Ikuko Yao1, Junko Iida1, Noriaki Tanaka2, and Yutaka Hata1

1 Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan, and 2 First Department of Surgery, Okayama University Medical School, Okayama 700-8558, Japan

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.

Key words: beta -catenin; synaptic scaffolding molecule; membrane-associated guanylate kinase with inverted domain organization; NMDA receptor; armadillo repeats; PDZ domain


Copyright © 2002 Society for Neuroscience  0270-6474/02/223757-09$05.00/0


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