Phospholipase C-gamma is required for agonist-induced Ca2+ entry
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- Phospholipase C-gamma is required for agonist-induced Ca2+ entry
- Patterson, RL; van Rossum, DB; Ford, DL; Hurt, KJ; Bae, SS; Suh, Pann-Ghill; Kurosaki, T; Snyder, SH; Gill, DL
- Issue Date
- CELL PRESS
- CELL, v.111, no.4, pp.529 - 541
- 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.
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