Research ArticleCell Biology

CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function

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Science Signaling  20 Apr 2021:
Vol. 14, Issue 679, eabc0425
DOI: 10.1126/scisignal.abc0425

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S1P signaling CLICs into place

The chloride intracellular channels CLIC1 and CLIC4 are implicated in vascular development, particularly in response to oxidative stress. Mao et al. found that these CLICs mediate the selective activation of small GTPases in response to the lipid second messenger S1P. In cultured endothelial cells, CLIC1 and CLIC4 together mediated S1P-induced Rac activation and downstream endothelial cell adhesion and sprouting, whereas CLIC1 alone mediated S1P-induced Rho activation and downstream endothelial stress fiber formation. The findings establish mechanisms in which these CLICs regulate endothelial cell function through both coordinated and distinct manners.

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