Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.

ABSTRACT: Volume-regulated anion channels (VRACs) formed by leucin-rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti-cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine-1-phosphate (S1P), an important signalling lipid, which signals through a fam

SUBMITTER: Kostritskaia Y 

PROVIDER: S-EPMC12333907 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature