TRPC channels as STIM1-regulated store-operated channels

Worley, Paul F.; Zeng, Weizhong; Huang, Guo N.; Yuan, Joseph P.; Kim, Joo Young; Lee, Min Goo; Muallem, Shmuel

doi:10.1016/j.ceca.2007.03.004

Cited by 200 publications

(185 citation statements)

References 59 publications

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“…The model does not rule out, however, that, even in the absence of cytosolic Ca 2ϩ , TRPCs may transition to the SOCE/ Icrac-gating mode via an intermediary mode in which they are associated with neither Orai nor STIM-Orai and gate in the nonselective ion channel mode. R3W mutants would reduce SOCE and ROCE by associating with and stabilizing the resting **Presence of TRPC3 mRNA in HEK293 cells is in full agreement with the fact that the cDNA encoding the human TRPC3 proteins was originally cloned from RNA isolated from these cells (10,24 figure 1A in ref. 14), given that, upon addition of the muscarinic receptor agonist carbachol to T3-9 cells, the nonselective current it elicited was transient.…”

Section: Discussionmentioning

confidence: 60%

“…As Ca 2ϩ stores are depleted, the store's Ca 2ϩ sensor STIM1 changes conformation with activation of a scaffolding function in its cytosolic C terminus. This promotes (i) the gradual reorganization and migration of Orai molecules into microdomains visible by confocal and total internal reflection fluorescence microscopy as puncta [described by Lewis and coworkers (20,21)], in which STIM and Orai colocalize; and (ii) the gradual migration of TRPCs to the same microdomains as a consequence of interacting with STIM activated by the Ca 2ϩ depletion process [described by Muallem, Worley, and coworkers (22)(23)(24)]. TRPCs associated with STIM-Orai complexes are proposed to be channels that operate in the SOCE/Icrac mode.…”

Section: Discussionmentioning

confidence: 99%

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Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels

Liao

Erxleben

Abramowitz

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

267

217

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Receptor-operated Ca 2؉ entry (ROCE) and store-operated Ca 2؉ entry (SOCE) into cells are functions performed by all higher eukaryotic cells, and their impairment is life-threatening. The main molecular components of this pathway appear to be known. However, the molecular make-up of channels mediating ROCE and SOCE is largely unknown. One hypothesis proposes SOCE channels to be formed solely by Orai proteins. Another proposes SOCE channels to be composed of both Orai and C-type transient receptor potential (TRPC) proteins. Both hypotheses propose that the channels are activated by STIM1, a sensor of the filling state of the Ca 2؉ stores that activates Ca 2؉ entry when stores are depleted. The role of Orai in SOCE has been proven. Here we show the TRPC-dependent reconstitution of Icrac, the electrophysiological correlate to SOCE, by expression of Orai1; we also show that R91W-Orai1 can inhibit SOCE and ROCE and that Orai1 and STIM1 expression leads to functional expression of Gd-resistant ROCE. Because channels that mediate ROCE are accepted to be formed with the participation of TRPCs, our data show functional interaction between ROCE and SOCE components. We propose that SOCE/Icrac channels are composed of heteromeric complexes that include TRPCs and Orai proteins.capacitative calcium entry ͉ signal transduction ͉ store depletion R eported independently by three laboratories at the beginning of 2006, Orai (also known as CRACM) proteins, especially Orai1, have emerged as the molecular candidates for the underlying structure of store-operated Ca 2ϩ entry (SOCE) channels responsible for the store-depletion activated Ca 2ϩ current, Icrac, without apparent role(s) for transient receptor potential ion channels (TRPCs) (reviewed in refs. 1-3). Before the discovery of Orai genes and their gene products, the only candidates presumed to underlie SOCE had been the members of the TRPC class of ion channels, of which there are seven. This proposition was based on primary research reports from many laboratories showing that expression of the cloned TRPCs enhances store-depletion activated Ca 2ϩ entry (cf. table 1.3 in ref. 4) and/or that injection of specific anti-TRPC antibodies or genetic ablation of TRPC genes reduces SOCE and/or Icrac. Moreover, Zagranichnaya et al. (5) showed partial reduction of SOCE in response to siRNAs that targeted TRPC1, TRPC3, or TRPC7, which, when combined, were partially additive. The idea promoted in the reviews listed above that channels responsible for SOCE and Icrac form without involvement of TRPC proteins is especially difficult to reconcile with the total loss of Icrac in vascular endothelial cells seen in TRPC4 knock-out mice (6) and the 80% loss of SOCE found in submaxillary acinar cells of TRPC1 knockout mice (7).Based on the foregoing data, and recognizing that Orai/ CRACMs are part of SOCE/Icrac channels, we proposed that SOCE/Icrac channels may be heteromeric complexes of TRPC and Orai proteins (8). If this were the case, we reasoned, expression of Orai1 in cells expressing excess ...

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels

Liao

Erxleben

Abramowitz

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

267

217

View full text Add to dashboard Cite

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“…Its interactions with the newly identified SOCE components, STIM1 and ORAI1, as a dynamic complex further amplify the physiological significance of TRPC1 as a SOC [41,46,47]. It is the status of the ER Ca 2+ store that regulates the activation of plasma membrane SOCs.…”

Section: Store-operated Calcium Entrymentioning

confidence: 99%

“…More recently, stromal interaction molecule (STIM) and ORAI [also known as calcium-release-activated calcium (CRAC) channels] proteins have been suggested as integral components of SOCE [39,40]. Predominantly in immune cells, ORAI1 constitutes the plasma membrane component of SOCs, whereas STIM1 functions as the ER Ca 2+ sensor which has a rather ubiquitous role in facilitation of SOCE by activating ORAI1 and/or TRPC (TRP canonical) components of SOCs [37,[39][40][41]. Although, the molecular identity of SOCs in keratinocytes remains elusive, increasing evidence suggests a profound involvement of TRPC channels in the skin system [42][43][44].…”

Section: Store-operated Calcium Entrymentioning

confidence: 99%

Darier’s disease: a calcium-signaling perspective

Pani

Singh

2007

Cell. Mol. Life Sci.

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Ca 2+ influx evoked across the plasma membrane upon internal store depletion is essential for a myriad of cellular functions including gene expression, cell proliferation, differentiation and even apoptosis. Darier's disease (DD), an autosomal dominant inherited disorder of the skin, arising due to mutations in the isoform 2 of the sarco (endo) plasmic reticulum Ca 2+ ATPase (SERCA2), exemplifies an anomaly of Ca 2+ signaling disturbances. Owing to loss of function mutations in SERCA2, keratinocytes in DD patients have a reduced pool of endoplasmic reticulum (ER) Ca 2+ . Importantly, the status of ER Ca 2+ is critical for the activation of a class of plasma membrane Ca 2+ channels referred to as store operated Ca 2+ channels (SOCs). The widely expressed transient receptor potential (TRP) family of channels is proposed to be SOCs. In this review we discuss DD from the viewpoint of Ca 2+ signaling and present a potential role for TRPC1 in the disease pathogenesis.

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“…STIM1 as well as Orai1 have been shown to interact with members of the canonical transient receptor potential channels, a family of phospholipase C regulated channels. 24,53,[90][91][92][93][94][95] Further studies are required to reveal the nature of SOCE channels in various tissues, possibly manifested by a combination of various Orai and TRP channels. This will clarify the contribution of STIM1 and Orai1 to SOCE in different tissues and will provide a more widespread view of store-operated channels and their physiological roles in health and disease.…”

Section: Channel Architecture Of Orai Channelsmentioning

confidence: 99%