The interaction of phospholipase C-beta3 with Shank2 regulates mGluR-mediated calcium signal.
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.
Hwang
Jong-Ik
JI
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
Kim
Hyeon Soo
HS
Lee
Jae Ran
JR
Kim
Eunjoon
E
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D020816:Amino Acid Motifs; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004926:Escherichia coli / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D054799:Phospholipase C beta; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D010738:Type C Phospholipases / Q000378:metabolism*
D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C485686:Shank2 protein, rat; C033652:postsynaptic density proteins; D005982:Glutathione Transferase; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518041:Plcb3 protein, rat; D019204:GTP-Binding Proteins; D002118:Calcium