Exp Biol Med (Maywood). 2009 Jun;234(6):673-82. doi: 10.3181/0809-RM-279. Epub 2009 Mar 23.

Interaction between TRPC1/TRPC4 assembly and STIM1 contributes to store-operated Ca2+ entry in mesangial cells.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Sours-Brothers, S., Ding, M., Graham, S., Ma, R.,
["Department of Integrative Physiology, University of North Texas Health Science Center, RES-302G, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA."]
Although Orai1 protein was recently identified as the component of CRAC channels in hematopoietic cells, store-operated channels (SOC) in other cell types may have a different molecular entity. Also, the activation mechanism of SOC remains unclear, in general. In the present study, we tested the hypothesis that TRPC1 and TRPC4 proteins were functional subunits of SOC in glomerular mesangial cells (MCs) and that STIM1 was required for the channel activation through interaction with the TRPC proteins. In cultured human MCs, cell-attached patch clamp and fura-2 fluorescence measurements showed that single knockdown of either TRPC1 or TRPC4 significantly attenuated thapsigargin-induced membrane currents and Ca2+ entry as well as Ang II-induced channel activity. Double knockdown of both TRPCs resulted in a comparable inhibition on store-operated Ca2+ entry with single knockdown of either TRPC. Consistent with our previous report, co-immunoprecipitation showed a physical interaction between TRPC1 and TRPC4. Furthermore, we found that knockdown of STIM1 using RNAi significantly reduced the thapsigargin-stimulated membrane currents. Co-immunoprecipitation showed that STIM1 interacted with TRPC4, but not TRPC1. In addition, simultaneous inhibition of STIM1 and TRPC1 resulted in a comparable effect on SOC with single inhibition of either one of them. Taken together, we conclude that in glomerular mesangial cells, the TRPC1/TRPC4 complexes constitute the functional subunits of SOC and that the interaction between STIM1 and TRPC4 may be the mechanism for the activation of the channels.
PMID: 19307462External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC4 Co-immunoprecipitation Human glomerular mesangial cell 19307462
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM1 Co-immunoprecipitation Human glomerular mesangial cell 19307462
TRPC4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunoprecipitation Human glomerular mesangial cell 19307462
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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