PMID:12547829

Citation	Smani, T, Zakharov, SI, Leno, E, Csutora, P, Trepakova, ES and Bolotina, VM (2003) Ca2+-independent phospholipase A2 is a novel determinant of store-operated Ca2+ entry. J. Biol. Chem. 278:11909-15
Abstract	Store-operated cation (SOC) channels and capacitative Ca(2+) entry (CCE) play very important role in cellular function, but the mechanism of their activation remains one of the most intriguing and long lasting mysteries in the field of Ca(2+) signaling. Here, we present the first evidence that Ca(2+)-independent phospholipase A(2) (iPLA(2)) is a crucial molecular determinant in activation of SOC channels and store-operated Ca(2+) entry pathway. Using molecular, imaging, and electrophysiological techniques, we show that directed molecular or pharmacological impairment of the functional activity of iPLA(2) leads to irreversible inhibition of CCE mediated by nonselective SOC channels and by Ca(2+)-release-activated Ca(2+) (CRAC) channels. Transfection of vascular smooth muscle cells (SMC) with antisense, but not sense, oligonucleotides for iPLA(2) impaired thapsigargin (TG)-induced activation of iPLA(2) and TG-induced Ca(2+) and Mn(2+) influx. Identical inhibition of TG-induced Ca(2+) and Mn(2+) influx (but not Ca(2+) release) was observed in SMC, human platelets, and Jurkat T-lymphocytes when functional activity of iPLA(2) was inhibited by its mechanism-based suicidal substrate, bromoenol lactone (BEL). Moreover, irreversible inhibition of iPLA(2) impaired TG-induced activation of single nonselective SOC channels in SMC and BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)-induced activation of whole-cell CRAC current in rat basophilic leukemia cells. Thus, functional iPLA(2) is required for activation of store-operated channels and capacitative Ca(2+) influx in wide variety of cell types.
Links	PubMed Online version:10.1074/jbc.M210878200
Keywords	Animals; Aorta/cytology; Blood Platelets/cytology; Blood Platelets/enzymology; Calcium/metabolism; Calcium Channels/metabolism; Group VI Phospholipases A2; Humans; Jurkat Cells; Manganese/pharmacokinetics; Membrane Potentials/drug effects; Membrane Potentials/physiology; Mice; Myocytes, Smooth Muscle/cytology; Myocytes, Smooth Muscle/enzymology; Naphthalenes/pharmacology; Oligonucleotides, Antisense/pharmacology; Patch-Clamp Techniques; Phosphodiesterase Inhibitors/pharmacology; Phospholipases A/genetics; Phospholipases A/metabolism; Phospholipases A2; Pyrones/pharmacology; Rabbits; Rats
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:PLPL9	involved_in	GO:1901339: regulation of store-operated calcium channel activity	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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