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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.