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Published April 1, 2005 | Published
Journal Article Open

The Interaction of Phospholipase C-{beta}3 with Shank2 Regulates mGluR-mediated Calcium Signal

Abstract

Phospholipase C-{beta} isozymes that are activated by G protein-coupled receptors (GPCR) and heterotrimeric G proteins carry a PSD-95/Dlg/ZO-1 (PDZ) domain binding motif at their C terminus. Through interactions with PDZ domains, this motif may endow the PLC-{beta} isozyme with specific roles in GPCR signaling events that occur in compartmentalized regions of the plasma membrane. In this study, we identified the interaction of PLC-{beta}3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-{beta}3, but not other PLC-{beta} isotypes, specifically interacts with the PDZ domain of Shank2. Homer 1b, a Shank-interacting protein that is linked to group I metabotropic glutamate receptors and IP3 receptors, forms a multiple complex with Shank2 and PLC-{beta}3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-{beta}3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-{beta}3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses.

Additional Information

© 2005 the American Society for Biochemistry and Molecular Biology. Received for publication, September 17, 2004, and in revised form, December 30, 2004. Originally published In Press as doi:10.1074/jbc.M410740200 on January 4, 2005. This study was supported by the National R & D Program for Fusion Strategy of Advanced Technologies of Ministry of Science & Technology (MOST) and by Korea Science and Engineering Foundation (KOSEF) through the Center for Cell Signaling Research at Ewha Womans University, Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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