Abstract
The mechanisms of agonist-induced calcium entry (ACE) following depletion of intracellular calcium stores have not been fully established. We report here that calcium-independent phospholipase A (iPLA(2)) is required for robust Ca(2+) entry in HaCaT keratinocytes following ATP or UTP stimulation. Lysophosphatidic acid (LPA), an unrelated agonist, evoked Ca(2+) release without inducing robust Ca(2+) entry. Both LPA and UTP induced the redistribution of STIM1 into puncta which localized to regions near or at the plasma membrane, as well as within the cytoplasm. Plasma membrane-associated STIM1 remained high for up to 10 min after UTP stimulation, whereas it had returned almost to baseline by that time point in LPA-stimulated cells. This correlated with faster reloading of the endoplasmic reticulum Ca(2+) stores in LPA treated cells. Thus by differentially regulating store-refilling after agonist-mediated depletion, LPA and UTP may exert distinct effects on the duration of STIM1 localization at the plasma membrane, and thus, on the magnitude and duration of ACE.