Phospholipase C-γ Is Required for Agonist-Induced Ca2+ Entry
Copyright policy )Phospholipase C-γ Is Required for Agonist-Induced Ca2+ Entry
We report here that PLC-gamma isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-gamma1 or a lipase-inactive mutant PLC-gamma1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-gamma1 was ineffective. RNA interference to deplete either PLC-gamma1 or PLC-gamma2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-gamma2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-gamma2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-gamma2 or a lipase-inactive PLC-gamma2 mutant. The results indicate a lipase-independent role of PLC-gamma in the physiological agonist-induced activation of Ca2+ entry.
- Johns Hopkins University United States
- Johns Hopkins Medicine United States
- University of Maryland, Baltimore United States
- UNIST (Ulsan National Institute of Science and Technology) Korea (Republic of)
- Johns Hopkins University School of Medicine United States
MECHANISM, STORE DEPLETION, ENDOPLASMIC-RETICULUM, CAPACITATIVE CALCIUM-ENTRY, PROTEIN, CALCIUM-ENTRY, PC12 Cells, Catalysis, ACTIVATION, Animals, Humans, RNA, Small Interfering, Cell Line, Transformed, RNA, Double-Stranded, TYROSINE PHOSPHORYLATION, RECEPTOR, Biochemistry, Genetics and Molecular Biology(all), Phospholipase C gamma, OPERATED HTRP3 CHANNELS, NECROTIC CELL-DEATH, C-GAMMA-1, Rats, Isoenzymes, Type C Phospholipases, Calcium, TRPC3 CHANNELS
MECHANISM, STORE DEPLETION, ENDOPLASMIC-RETICULUM, CAPACITATIVE CALCIUM-ENTRY, PROTEIN, CALCIUM-ENTRY, PC12 Cells, Catalysis, ACTIVATION, Animals, Humans, RNA, Small Interfering, Cell Line, Transformed, RNA, Double-Stranded, TYROSINE PHOSPHORYLATION, RECEPTOR, Biochemistry, Genetics and Molecular Biology(all), Phospholipase C gamma, OPERATED HTRP3 CHANNELS, NECROTIC CELL-DEATH, C-GAMMA-1, Rats, Isoenzymes, Type C Phospholipases, Calcium, TRPC3 CHANNELS
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