The interaction of phospholipase C-β3 with Shank2 regulates mGluR-mediated calcium signal

Jong-Ik Hwang, Hyeon Soo Kim, Ran Lee Jae, Eunjoon Kim, Ho Ryu Sung, Pann Ghill Suh

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Phospholipase C-β 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-β 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-β3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-β3, but not other PLC-β 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-β3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-β3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-β3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses.

Original languageEnglish
Pages (from-to)12467-12473
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
Publication statusPublished - 2005 Apr 1
Externally publishedYes

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Post-Synaptic Density
Type C Phospholipases
Programmable logic controllers
G-Protein-Coupled Receptors
Calcium
Isoenzymes
Inositol 1,4,5-Trisphosphate Receptors
Heterotrimeric GTP-Binding Proteins
Metabotropic Glutamate Receptors
Microinjections
Synapses
Cell Membrane
Peptides
Cell membranes
Scaffolds
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

The interaction of phospholipase C-β3 with Shank2 regulates mGluR-mediated calcium signal. / Hwang, Jong-Ik; Kim, Hyeon Soo; Jae, Ran Lee; Kim, Eunjoon; Sung, Ho Ryu; Suh, Pann Ghill.

In: Journal of Biological Chemistry, Vol. 280, No. 13, 01.04.2005, p. 12467-12473.

Research output: Contribution to journalArticle

Hwang, Jong-Ik ; Kim, Hyeon Soo ; Jae, Ran Lee ; Kim, Eunjoon ; Sung, Ho Ryu ; Suh, Pann Ghill. / The interaction of phospholipase C-β3 with Shank2 regulates mGluR-mediated calcium signal. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 13. pp. 12467-12473.
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