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

Research output: Contribution to journalArticlepeer-review

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

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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