Phospholipase C-γ is required for agonist-induced Ca2+ entry

Randen L. Patterson, Damian B. Van Rossum, Diana L. Ford, Kenneth J. Hurt, Sun Sik Bae, Pann Ghill Suh, Tomohiro Kurosaki, Solomon H. Snyder, Donald L. Gill

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162 Scopus citations

Abstract

We report here that PLC-γ isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-γ1 or a lipase-inactive mutant PLC-γ1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-γ1 was ineffective. RNA interference to deplete either PLC-γ1 or PLC-γ2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-γ2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-γ2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-γ2 or a lipase-inactive PLC-γ2 mutant. The results indicate a lipase-independent role of PLC-γ in the physiological agonist-induced activation of Ca2+ entry.

Original languageEnglish (US)
Pages (from-to)529-541
Number of pages13
JournalCell
Volume111
Issue number4
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Patterson, R. L., Van Rossum, D. B., Ford, D. L., Hurt, K. J., Bae, S. S., Suh, P. G., Kurosaki, T., Snyder, S. H., & Gill, D. L. (2002). Phospholipase C-γ is required for agonist-induced Ca2+ entry. Cell, 111(4), 529-541. https://doi.org/10.1016/S0092-8674(02)01045-0