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-beta3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-beta3, 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-beta3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-beta3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-beta3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Binding, Competitive
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COS Cells
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Calcium / metabolism*
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Carrier Proteins / chemistry
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Cell Membrane / metabolism
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Cells, Cultured
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Disks Large Homolog 4 Protein
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Escherichia coli / metabolism
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GTP-Binding Proteins / chemistry
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Gene Expression Regulation*
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Glutathione Transferase / metabolism
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Hippocampus / metabolism
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Homer Scaffolding Proteins
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Immunohistochemistry
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Immunoprecipitation
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Intracellular Signaling Peptides and Proteins
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Isoenzymes / metabolism*
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Membrane Proteins
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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Peptides / chemistry
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Phospholipase C beta
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Plasmids / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Rats
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Receptors, Metabotropic Glutamate / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Synapses / metabolism
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Transfection
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Two-Hybrid System Techniques
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Type C Phospholipases / metabolism*
Substances
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Carrier Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Homer Scaffolding Proteins
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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Membrane Proteins
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Nerve Tissue Proteins
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Peptides
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Receptors, Metabotropic Glutamate
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Recombinant Fusion Proteins
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Shank2 protein, rat
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postsynaptic density proteins
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Glutathione Transferase
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Type C Phospholipases
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Phospholipase C beta
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Plcb3 protein, rat
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GTP-Binding Proteins
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Calcium