Author/Authors :
Randen L. Patterson، نويسنده , , Damian B. van Rossum، نويسنده , , Diana L. Ford، نويسنده , , Kenneth J. Hurt، نويسنده , , Sun Sik Bae، نويسنده , , Pann-Ghill Suh، نويسنده , , Tomohiro Kurosaki، نويسنده , , Solomon H. Snyder، نويسنده , , Donald L. Gill، نويسنده ,
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.
