A novel mechanism for the store-operated calcium influx pathway

Csutora, Peter; Leno, Endri; Sergey I. Zakharov, Endri; Smani, Tarik; Trepakova, Elena S.; Bolotina, Victoria M.
February 2004
Nature Cell Biology;Feb2004, Vol. 6 Issue 2, following p113
Academic Journal
Activation of store-operated channels (SOCs) and capacitative calcium influx are triggered by depletion of intracellular calcium stores. However, the exact molecular mechanism of such communication remains unclear. Recently, we demonstrated that native SOC channels can be activated by calcium influx factor (CIF) that is produced upon depletion of calcium stores, and showed that Ca2+-independent phospholipase A2 (iPLA2) has an important role in the store-operated calcium influx pathway. Here, we identify the key plasma-membrane-delimited events that result in activation of SOC channels. We also propose a novel molecular mechanism in which CIF displaces inhibitory calmodulin (CaM) from iPLA2, resulting in activation of iPLA2 and generation of lysophospholipids that in turn activate soc channels and capacitative calcium influx. Upon refilling of the stores and termination of CIF production, CaM rebinds to iPLA2, inhibits it, and the activity of SOC channels and capacitative calcium influx is terminated.


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