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.
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."]
["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: 20093626

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Validation: In vivo validation
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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 |
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TRPV4 | Co-immunofluorescence staining | HEK293 | Human | Full-length | Mouse | Full-length | 20093626 | |
TRPC1 |
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TRPV4 | Co-immunofluorescence staining | Rat mesenteric artery endothelial cell lysates | 20093626 | |||||
TRPC1 |
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TRPV4 | Fluorescence resonance energy transfer | HEK293 | Human | Full-length | Mouse | Full-length | 20093626 | |
TRPC1 |
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TRPV4 | Co-immunoprecipitation | HEK293 | Human | Full-length | Mouse | Full-length | 20093626 | |
TRPC1 |
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TRPV4 | Co-immunoprecipitation | Rat mesenteric artery endothelial cell lysates | 20093626 | |||||
TRPV4 |
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TRPC1 | Co-immunofluorescence staining | HEK293 | Mouse | Full-length | Human | Full-length | 20093626 | |
TRPV4 |
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TRPC1 | Co-immunofluorescence staining | Rat mesenteric artery endothelial cell lysates | 20093626 | |||||
TRPV4 |
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TRPC1 | Fluorescence resonance energy transfer | HEK293 | Mouse | Full-length | Human | Full-length | 20093626 | |
TRPV4 |
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TRPC1 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Human | Full-length | 20093626 | |
TRPV4 |
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TRPC1 | Co-immunoprecipitation | Rat mesenteric artery endothelial cell lysates | 20093626 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Functional consequence
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPV4 |
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TRPC1 | Calcium measurement | Activation | 20093626 |
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:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
