Fast endocytic recycling determines TRPC1–STIM1 clustering in ER–PM junctions and plasma membrane function of the channel

Souza, Lorena Brito de; Ong, Hwei Ling; Liu, Xibao; Ambudkar, Indu S.

doi:10.1016/j.bbamcr.2015.07.019

Cited by 28 publications

(24 citation statements)

References 56 publications

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“…Importantly, co-expression of Rab4 with Rab5, but not STIM1 or Rab11, rescued routing of TRPC1 to the plasma membrane (recovery of TRPC1 function shown in Figure 1C). Notably, while STIM1 is required for recruitment of TRPC1 into the plasma membrane and activation after cell stimulation, it is not involved in intracellular trafficking of the channel [75]. This study also showed that internalization of TRPC1 occurs via an endocytic pathway mediated by ARF6 that is independent of clathrin and Cav-1.…”

Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 64%

“…Internalization of TRPC1 from the plasma membrane, and its transport to this region, is determined by endocytic and exocytic vesicular trafficking pathways, respectively. A recent study has identified the essential vesicular compartments and Rab proteins involved in regulating intracellular trafficking of TRPC1 [75]. This study demonstrated that TRPC1 is trafficked via a fast endocytic recycling pathway which involves Rab5 and Rab4 (Figure 2A–C).…”

Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 74%

“…More importantly, the effects of Rab5 and Arf6 were highly specific for TRPC1, leaving Orai1 and STIM1 unaffected. Generation of the TRPC1-mediated I SOC was suppressed in HSG cells expressing either Rab5 or ARF6, resulting instead in the generation of the Orai1-mediated I CRAC [75]. A very interesting observation reported in this paper was that under conditions when TRPC1 is inserted into the membrane and activated by STIM1, I SOC current is generated in response to ER-Ca 2+ store depletion, while conditions that block TRPC1 trafficking to the plasma membrane results in generation of I CRAC .…”

Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 99%

“…Ca 2+ entry via Orai1 triggers recruitment of TRPC1 from Rab4-vesicles into the plasma membrane, where the channel interacts with STIM1 and is activated. Thus, endocytic recycling via Rab4 determines clustering of TRPC1with STIM1, as well as plasma membrane insertion and function of the channel (Modified from [75]). B–C .…”

Section: Figurementioning

confidence: 99%

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TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces

2017

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Store-operated calcium entry (SOCE) is a ubiquitous Ca2+ entry pathway that is activated in response to depletion of ER-Ca2+ stores and critically controls the regulation of physiological functions in miscellaneous cell types. The transient receptor potential canonical 1 (TRPC1) is the first member of the TRPC channel subfamily to be identified as a molecular component of SOCE. While TRPC1 has been shown to contribute to SOCE and regulate various functions in many cells, none of the reported TRPC1-mediated currents resembled ICRAC, the highly Ca2+-selective store-dependent current first identified in lymphocytes and mast cells. Almost a decade after the cloning of TRPC1 two proteins were identified as the primary components of the CRAC channel. The first, STIM1, is an ER-Ca2+ sensor protein involved in activating SOCE. The second, Orai1 is the pore-forming component of the CRAC channel. Co-expression of STIM1 and Orai1 generated robust ICRAC. Importantly, STIM1 was shown to also activate TRPC1 via its C-terminal polybasic domain, which is distinct from its Orai1-activating domain, SOAR. In addition, TRPC1 function critically depends on Orai1-mediated Ca2+ entry which triggers recruitment of TRPC1 into the plasma membrane where it is then activated by STIM1. More importantly, TRPC1 and Orai1 form discrete STIM1-gated channels that generate distinct Ca2+ signals and regulate specific cellular functions. Surface expression of TRPC1 can be modulated by trafficking of the channel to and from the plasma membrane, resulting in changes to the phenotype of TRPC1-mediated current and [Ca2+]i signals. Thus, TRPC1 is activated downstream of Orai1 and modifies the initial [Ca2+]i signal generated by Orai1 following store depletion. This review will summarize the important findings that underlie the current concepts for activation and regulation of TRPC1, as well as its impact on cell function.

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Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 64%

Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 74%

Section: Modulation Of Trpc1 Expression and Activity At The Plasma Mementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces

2017

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“…; de Souza et al. ). Calcium influx through Orai and direct interactions between STIM and TRPC1 regulates the delivery of TRPC1 channels to specific domains within the plasma membrane (Ong et al.…”

Section: Discussionmentioning

confidence: 97%

Orai and TRPC channel characterization in FcεRI‐mediated calcium signaling and mediator secretion in human mast cells

Wajdner

Farrington

Barnard

et al. 2017

Physiological Reports

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Inappropriate activation of mast cells via the Fcε RI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to Fcε RI‐initiated mediator release. However, until now the role of TRPC calcium channels in Fcε RI‐mediated human mast cell signaling has not been published. Here, we show evidence for the expression of Orai 1,2, and 3 and TRPC1 and 6 in primary human lung mast cells and the LAD2 human mast cell line but, we only find evidence of functional contribution of Orai and not TRPC channels to Fcε RI‐mediated calcium entry. Calcium imaging experiments, utilizing an Orai selective antagonist (Synta66) showed the contribution of Orai to Fcε RI‐mediated signaling in human mast cells. Although, the use of a TRPC3/6 selective antagonist and agonist (GSK‐3503A and GSK‐2934A, respectively) did not reveal evidence for TRPC6 contribution to Fcε RI‐mediated calcium signaling in human mast cells. Similarly, inactivation of STIM1‐regulated TRPC1 in human mast cells (as tested by transfecting cells with STIM1‐KK 684‐685 EE ‐ TRPC1 gating mutant) failed to alter Fcε RI‐mediated calcium signaling in LAD2 human mast cells. Mediator release assays confirm that Fcε RI‐mediated calcium influx through Orai is necessary for histamine and TNF α release but is differentially involved in the generation of cytokines and eicosanoids.

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Functional differences in agonist‐induced plasma membrane expression of Orai1α and Orai1β

Jardín

Alvarado

Sánchez-Collado

et al. 2023

Journal Cellular Physiology

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Orai1 is the pore‐forming subunit of the store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels involved in a variety of cellular functions. Two Orai1 variants have been identified, the long form, Orai1α, containing 301 amino acids, and the short form, Orai1β, which arises from alternative translation initiation from methionines 64 or 71, in Orai1α. Orai1 is mostly expressed in the plasma membrane, but a subset of Orai1 is located in intracellular compartments. Here we show that Ca2+ store depletion leads to trafficking and insertion of compartmentalized Orai1α in the plasma membrane via a mechanism that is independent on changes in cytosolic free‐Ca2+ concentration, as demonstrated by cell loading with the fast intracellular Ca2+ chelator dimethyl BAPTA in the absence of extracellular Ca2+. Interestingly, thapsigargin (TG) was found to be unable to induce translocation of Orai1β to the plasma membrane when expressed individually; by contrast, when Orai1β is co‐expressed with Orai1α, cell treatment with TG induced rapid trafficking and insertion of compartmentalized Orai1β in the plasma membrane. Translocation of Orai1 forms to the plasma membrane was found to require the integrity of the actin cytoskeleton. Finally, expression of a dominant negative mutant of the small GTPase ARF6, and ARF6‐T27N, abolished the translocation of compartmentalized Orai1 variants to the plasma membrane upon store depletion. These findings provide new insights into the mechanism that regulate the plasma membrane abundance of Orai1 variants after Ca2+ store depletion.

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Fast endocytic recycling determines TRPC1–STIM1 clustering in ER–PM junctions and plasma membrane function of the channel

Cited by 28 publications

References 56 publications

TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces

TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces

Orai and TRPC channel characterization in FcεRI‐mediated calcium signaling and mediator secretion in human mast cells

Functional differences in agonist‐induced plasma membrane expression of Orai1α and Orai1β

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