Relocalization of STIM1 for Activation of Store-operated Ca2+ Entry Is Determined by the Depletion of Subplasma Membrane Endoplasmic Reticulum Ca2+ Store

Abstract

entering the cell is rapidly taken up into the ER by SERCA activity with minimal diffusion in the subplasma membrane region. These studies indicate close apposition of the ER and plasma membrane at the site of SOCE (1-6). Thus, it has been suggested that ER localized in the subplasma membrane region is likely to be coupled to SOCE and that depletion of these local Ca 2ϩ stores triggers activation of SOCE. The presently proposed mechanisms for activation of SOCE suggest direct physical coupling between components in the ER and plasma membrane, generation of diffusible components, or recruitment of the SOC channel. The exact mechanism involved in regulation of SOCE as well as the molecular components of the channel(s) mediating Ca 2ϩ entry in different types of cells has not been clearly identified.Recent studies have suggested STIM1 (stromal interacting molecule 1) as a novel regulator for SOCE. STIM1, which is a Ca 2ϩ -binding protein localized diffusely in the ER, has been shown to relocate into a peripheral region of the cell in response to internal Ca 2ϩ store depletion (7,8). STIM1 displays punctate subplasma membrane localization in response to depletion of intracellular Ca 2ϩ stores, which has been reported to be causal in activation of SOCE and to define the elementary unit that is involved in SOCE. Although several studies have clearly established involvement of ER-plasma membrane junctional domains in the regulation of SOCE, the exact site of store depletion has not yet been demonstrated. Based on all of the data available presently, it is logical to propose that that since the EF-hand domain of STIM1 is localized in the lumen of the ER and STIM1 punctae involved in SOCE activation are localized in subplasma membrane Ca 2ϩ stores very close to the surface * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1

“…Our previous studies and several other reports (5,6,9,10,22,(26)(27)(28) provide strong evidence that the microdomains involved in regulation of TRPC1-SOCE are plasma membrane LRD. Here we show that TRPC1 clusters with Cav1 in LRD before stimulation of the cells while after Ca 2ϩ -store depletion, the channel clusters with STIM1.…”

“…Ca 2ϩ depletion in the ER lumen is detected by the Ca 2ϩ -binding protein STIM1, which oligomerizes into puncta and relocates to discrete ERplasma membrane (ER-PM) junctional regions (2,3) where it associates with and activates store-operated channels including Orai1 and TRPC1, which are components of CRAC and SOC channels, respectively (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Therefore, the location of these channels in the plasma membrane is likely to be critical for their interaction with peripheral STIM1 and activation.…”

TLR-Mediated Secretion of Endoplasmic Reticulum Aminopeptidase 1 from Macrophages

“…*p , 0.05, **p , 0.01, ***p , 0.001. marker ( Fig. 6B) (28). Treatment with 2 mM thapsigargin for 4 h caused redistribution, which could be an indicator of Ca 2+ influx into the cells because STIM1 activates the store-operated Ca 2+ channel Orai1 in the cell membrane (29).…”

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

“…After STIM relocation at the PM-SR junctions, STIM interact physically with the Orai channels at the plasma membrane and activate Ca 2+ entry (Fig. 2E) (Liou et al, 2005;Zhang et al, 2005;Prakriya et al, 2006;Ong et al, 2007;Muik et al, 2008;Navarro-Borelly et al, 2008;Park et al, 2009a;Zheng et al, 2013a). Recently, the store operated channel entry associated regulatory factor was found to associate with STIM at the plasma membrane so as to regulate calcium influx via Orai to avoid excessive refill of the SR (Palty et al, 2012).…”