title: Cytosolic Ca2+ prevents the subplasmalemmal clustering of STIM1: an intrinsic mechanism to avoid Ca2+ overload.
abstract: The stromal interacting molecule (STIM1) is pivotal for store-operated Ca(2+) entry (SOC). STIM1 proteins sense the Ca(2+) concentration within the lumen of the endoplasmic reticulum (ER) via an EF-hand domain. Dissociation of Ca(2+) from this domain allows fast oligomerization of STIM1 and the formation of spatially discrete clusters close to the plasma membrane. By lifetime-imaging of STIM1 interaction, the rearrangement of STIM1, ER Ca(2+) concentration ([Ca(2+)](ER)) and cytosolic Ca(2+) signals ([Ca(2+)](cyto)) we show that [Ca(2+)](cyto) affects the subcellular distribution of STIM1 oligomers and prevents subplasmalemmal STIM clustering, even if the ER is depleted. These data indicate that [Ca(2+)](cyto), independently of the ER Ca(2+) filling state, crucially tunes the formation and disassembly of subplasmalemmal STIM1 clusters, and, thus, protects cells against Ca(2+) overload resulting from excessive SOC activity.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Malli
authors.forename: Shamim
authors.initials: S
authors.lastname: Naghdi
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier