Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):851-8. doi: 10.1161/ATVBAHA.109.196584. Epub 2010 Jan 21.

Functional role of vanilloid transient receptor potential 4-canonical transient receptor potential 1 complex in flow-induced Ca2+ influx.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Ma, X., Qiu, S., Luo, J., Ma, Y., Ngai, C. Y., Shen, B., Wong, C. O., Huang, Y., Yao, X.,
["Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China."]
OBJECTIVE: The present study is aimed at investigating the interaction of TRPV4 with TRPC1 and the functional role of such an interaction in flow-induced Ca(2+) influx. Hemodynamic blood flow is an important physiological factor that modulates vascular tone. One critical early event in this process is a cytosolic Ca(2+) ([Ca(2+)](i)) rise in endothelial cells in response to flow. METHODS AND RESULTS: With the use of fluorescence resonance energy transfer, coimmunoprecipitation, and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a complex. In functional studies, flow elicited a transient [Ca(2+)](i) increase in TRPV4-expressing human embryonic kidney (HEK) 293 cells. Coexpression of TRPC1 with TRPV4 markedly prolonged this [Ca(2+)](i) transient; it also enabled this [Ca(2+)](i) transient to be negatively modulated by protein kinase G. Furthermore, this flow-induced [Ca(2+)](i) increase was markedly inhibited by anti-TRPC1-blocking antibody T1E3 and a dominant-negative construct TRPC1 Delta 567-793 in TRPV4-C1-coexpressing HEK cells and human umbilical vein endothelial cells. T1E3 also inhibited flow-induced vascular dilation in isolated rat small mesenteric artery segments. CONCLUSIONS: This study shows that TRPC1 interacts physically with TRPV4 to form a complex, and this TRPV4-C1 complex may mediate flow-induced Ca(2+) influx in vascular endothelial cells. The association of TRPC1 with TRPV4 prolongs the flow-induced [Ca(2+)](i) transient, and it also enables this [Ca(2+)](i) transient to be negatively modulated by protein kinase G. This TRPV4-C1 complex plays a key role in flow-induced endothelial Ca(2+) influx.
PMID: 20093626External 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
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 TRPV4 Co-immunofluorescence staining HEK293 Human Full-length Mouse Full-length 20093626
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPV4 Co-immunofluorescence staining Rat mesenteric artery endothelial cell lysates 20093626
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPV4 Fluorescence resonance energy transfer HEK293 Human Full-length Mouse Full-length 20093626
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPV4 Co-immunoprecipitation HEK293 Human Full-length Mouse Full-length 20093626
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPV4 Co-immunoprecipitation Rat mesenteric artery endothelial cell lysates 20093626
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunofluorescence staining HEK293 Mouse Full-length Human Full-length 20093626
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunofluorescence staining Rat mesenteric artery endothelial cell lysates 20093626
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Fluorescence resonance energy transfer HEK293 Mouse Full-length Human Full-length 20093626
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunoprecipitation HEK293 Mouse Full-length Human Full-length 20093626
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunoprecipitation Rat mesenteric artery endothelial cell lysates 20093626
(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
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV4 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Calcium measurement Activation 20093626
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

To prevent spam comments, we use reCAPTCHA. Please type correct words into the following box.