A GPRC5B-Fyn signaling axis regulates VRAC activity by targeting LRRC8A.

GPRC5B-Fyn signaling axis regulates VRAC activity by targeting LRRC8A at Y362 in astrocytes and reconstituted systems.

• Why it matters: Understanding how physiological signals control VRAC is crucial because its dysregulation is linked to diseases like megalencephalic leukoencephalopathy.
• What they did: The study identified that GPRC5B binds LRRC8A and recruits Fyn kinase, which suppresses VRAC activation through Y362 phosphorylation, with disruption of this interaction abolishing inhibition.
• The result: This reveals a receptor-kinase-channel pathway that modulates VRAC activity via Y362, providing a molecular basis for VRAC regulation and its potential role in disease mechanisms.