Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells

Lièvremont, Jean-Philippe; Bird, Gary S.; Putney, James W.

doi:10.1152/ajpcell.00350.2004

Cited by 82 publications

(91 citation statements)

References 50 publications

(54 reference statements)

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“…Thus, when TRPC3 channels are expressed in excess, they respond differently to receptor activation of phospholipase C and to store depletion. These results have also been interpreted as evidence for the idea that homomeric (over expressed) TRPC3 channels are insensitive to store depletion (18,19,23,43). Alternatively, we hypothesized that the regulatory sites with which diacylglycerol and protein kinase C need to interact to affect Ca 2ϩ entry are not accessible under physiologic conditions because binding of Orai occludes them.…”

Section: Resultsmentioning

confidence: 88%

“…When expressed in model cells they form calcium-permeable, largely nonselective cation channels (12,13). Most of the TRPCs have been shown either to be activated by store depletion or to be essential components of SOCE, including TRPC1 (14,15), TRPC2 (16,17), TRPC3 (18,19), TRPC4 (20), TRPC5 (21), and TRPC7 (22,23). Gene inactivation (24) and RNAi (25) studies also support a role for TRPCs in SOCE.…”

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confidence: 99%

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Orai proteins interact with TRPC channels and confer responsiveness to store depletion

Liao¹,

Erxleben

Yildirim³

et al. 2007

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

277

232

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The TRPC (C-type transient receptor potential) class of ion channels has been hypothesized to participate in store-operated Ca 2؉ entry (SOCE). Recently, however, STIM1 and Orai1 proteins have been proposed to form SOCE channels. Whether TRPCs participate in SOCE that is dependent on or regulated by Orai has not been explored. Here we show that Orai1 physically interacts with the N and C termini of TRPC3 and TRPC6, and that in cells overexpressing either TRPC3 or TRPC6 in a store-depletion insensitive manner, these TRPCs become sensitive to store depletion upon expression of an exogenous Orai. Thus, Orai-1, -2, and -3 enhanced thapsigargin-induced calcium entry by 50 -150% in cells stably overexpressing either TRPC3 or TRPC6. Orai1 expression had no significant effect on endogenous, thapsigargin-induced calcium entry in wildtype cells (HEK-293, COS1), in HEK cells expressing a thapsigarginsensitive variant of TRPC3 (TRPC3a), or in HEK cells overexpressing another membrane protein, V1aR. Single-channel cation currents present in membrane patches of TRPC3-overexpressing cells were suppressed by expression of Orai1. We propose that Orai proteins by interacting with TRPCs act as regulatory subunits that confer STIM1-mediated store depletion sensitivity to these channels.capacitative calcium entry ͉ ion channels ͉ thapsigargin ͉ transmembrane signaling

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Section: Resultsmentioning

confidence: 88%

mentioning

confidence: 99%

Orai proteins interact with TRPC channels and confer responsiveness to store depletion

Liao¹,

Erxleben

Yildirim³

et al. 2007

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

277

232

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“…Number of reports has shown a reduced SOCE activity when TRPC expression was knocked down or knocked out [8][9][10][11]. When exogenously expressed some TRPC channels displayed SOCE activity [12][13][14]. However, numerous studies also demonstrated that TRPC channels did not operate as SOCE channels, but rather are gated by second messengers like Ca 2+ or diacylglycerol (DAG; [15][16][17]).…”

Section: Introductionmentioning

confidence: 99%

“…However, numerous studies also demonstrated that TRPC channels did not operate as SOCE channels, but rather are gated by second messengers like Ca 2+ or diacylglycerol (DAG; [15][16][17]). Hence, the involvement of TRPC channels in the SOCE mechanism is a controversial issue, and appears to dependent on the cell types investigated, and importantly on the expression level of the TRPC [14,18,19].…”

Section: Introductionmentioning

confidence: 99%

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

et al. 2011

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a b s t r a c tThe ER Ca 2+ sensor STIM1 and the Ca 2+ channel Orai1 are key players in store-operated Ca 2+ entry (SOCE). In addition, channels from the TRPC family were also shown to be engaged during SOCE, while their precise implication remains controversial. In this study, we investigated the molecular players involved in SOCE triggered by the SERCA pump inhibitor thapsigargin in an endothelial cell line, the EA.hy926. siRNA directed against STIM1 or Orai1 reduced Ca 2+ entry by about 50-60%, showing that a large part of the entry is independent from these proteins. Blocking the PLC or the PKC pathway completely abolished thapsigargin-induced Ca 2+ entry in cells depleted from STIM1 and/or Orai1. The phorbol ester PMA or the DAG analog OAG restored the Ca 2+ entry inhibited by PLC blockers, showing an involvement of PLC/PKC pathway in SOCE. Using pharmacological inhibitors or siRNA revealed that the PKCeta is required for Ca 2+ entry, and pharmacological inhibition of the tyrosine kinase Src also reduced Ca 2+ entry. TRPC3 silencing diminished the entry by 45%, while the double STIM1/TRPC3 invalidation reduced Ca 2+ entry by more than 85%. Hence, in EA.hy926 cells, TG-induced Ca 2+ entry results from the activation of the STIM1/Orai1 machinery, and from the activation of TRPC3.

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“…Philipp et al (8) and Freichel et al (9) reported store-depletion-induced activation of TRPC4, and Philipp et al (10) were able to activate TRPC5 in transfected cells. Riccio et al (11) and, more recently, Livremont et al (12) have reported activation by store depletion of TRPC7 expressed in cultured cells. In contrast, studying TRPC3, Schultz and coworkers (13), Kamouchi et al (14), and we (unpublished data) have been unable to activate this channel by inhibition of endogenous sarcoplasmic-endoplasmic reticulum Ca 2ϩ pumps with thapsigargin without concurrent activation of PLC or addition of IP3.…”

mentioning

confidence: 97%

Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel

Yildirim

Kawasaki²,

Birnbaumer³

2005

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

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AK032317 is the GenBank accession no. of a full-length RIKEN mouse cDNA. It encodes a putative variant of the C3-type TRPC (transient receptor potential channel) that differs from the previously cloned murine TRPC3 cDNA in that it has a 5 extension stemming from inclusion of an additional exon (exon 0). The extended cDNA adds 62 aa to the sequence of the murine TRPC3. Here, we report the cloning of a cDNA encoding the human homologue of this extended TRPC3 having a highly homologous 73-aa N-terminal extension, referred to as hTRPC3a. A query of the GenBank genomic database predicts the existence of a similar gene product also in rats. Transient expression of the longer TRPC3a in human embryonic kidney (HEK) cells showed that it mediates Ca 2؉ entry in response to stimulation of the Gq-phospholipase C ␤ pathway, which is similar to that mediated by the shorter hTRPC3. However, after isolation of HEK cells expressing hTRPC3 in stable form, TRPC3a gave rise to Ca 2؉ -entry channels that are not only activated by the Gq-phospholipase C ␤ pathway (receptor-activated Ca entry) but also by thapsigargin triggered store depletion. In conjunction with findings from our and other laboratories that TRPC1, TRPC2, TRPC4, TRPC5, and TRPC7, can each mediate storedepletion-activated Ca 2؉ entry in mammalian cells, our findings with hTRC3a support our previous proposal that TRPCs form capacitative Ca-entry channels.capacitative Ca entry ͉ cation channel ͉ store-operated Ca entry

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Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells

Abstract: . Canonical transient receptor potential TRPC7 can function as both receptor-and store-operated channel in HEK-293 cells.

Cited by 82 publications

References 50 publications

Orai proteins interact with TRPC channels and confer responsiveness to store depletion

Orai proteins interact with TRPC channels and confer responsiveness to store depletion

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel

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