Agonist-induced calcium entry correlates with STIM1 translocation.
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.
Ross
Kehinde
K
Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom. Kehinde.Ross@newcastle.ac.uk
Whitaker
Michael
M
Reynolds
Nick J
NJ
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054522:Group VI Phospholipases A2; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D000071737:Stromal Interaction Molecule 1; D014544:Uridine Triphosphate / Q000494:pharmacology*
D008246:Lysophospholipids; D008565:Membrane Proteins; D009281:Naphthalenes; D009363:Neoplasm Proteins; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; C032881:lysophosphatidic acid; D002118:Calcium; D014544:Uridine Triphosphate