Biochim Biophys Acta. 2012 Aug;1823(8):1242-51. doi: 10.1016/j.bbamcr.2012.05.023. Epub 2012 May 26.

Capacitative and non-capacitative signaling complexes in human platelets.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Berna-Erro, A., Galan, C., Dionisio, N., Gomez, L. J., Salido, G. M., Rosado, J. A.,
["Department of Physiology, University of Extremadura, Caceres, Spain."]
Discharge of the intracellular Ca(2+) stores activates Ca(2+) entry through store-operated channels (SOCs). Since the recent identification of STIM1 and STIM2, as well as the Orai1 homologs, Orai2 and Orai3, the protein complexes involved in Ca(2+) signaling needs re-evaluation in native cells. Using real time PCR combined with Western blotting we have found the expression of the three Orai isoforms, STIM1, STIM2 and different TRPCs in human platelets. Depletion of the intracellular Ca(2+) stores with thapsigargin, independently of changes in cytosolic Ca(2+) concentration, enhanced the formation of a signaling complex involving STIM1, STIM2, Orai1, Orai2 and TRPC1. Furthermore, platelet treatment with the dyacylglicerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) resulted in specific association of Orai3 with TRPC3. Treatment of platelets with arachidonic acid enhanced the association between Orai1 and Orai3 in human platelets and overexpression of Orai1 and Orai3 in HEK293 cells increased arachidonic acid-induced Ca(2+) entry. These results indicate that Ca(2+) store depletion results in the formation of exclusive signaling complexes involving STIM proteins, as well as Orai1, Orai2 and TRPC1, but not Orai3, which seems to be involved in non-capacitative Ca(2+) influx in human platelets.
PMID: 22640869External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai2 Speculation Prediction 22640869
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai3 Speculation Prediction 22640869
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM2 Speculation Prediction 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM1 Speculation Prediction 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM2 Speculation Prediction 22640869
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai2 Speculation Prediction 22640869
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai3 Speculation Prediction 22640869
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Screening Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vitro validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Validation: In vivo validation Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Characterization Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b Functional consequence Arrow2 1fb2b8a5ad55723bad55961567d092af30310a7cf44ded6f695fc2aa4753ec2b top
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 Orai2 Co-immunoprecipitation Human platelets 22640869
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai3 Co-immunoprecipitation Human platelets 22640869
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM2 Co-immunoprecipitation Human platelets 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai2 Co-immunoprecipitation Human platelets 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai3 Co-immunoprecipitation Human platelets 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM1 Co-immunoprecipitation Human platelets 22640869
TRPC3 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 STIM2 Co-immunoprecipitation Human platelets 22640869
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai2 Co-immunoprecipitation Human platelets 22640869
TRPC6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Orai3 Co-immunoprecipitation Human platelets 22640869
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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