Coupling between protein condensates and ordered membrane domains facilitate T cell activation

Liquid-liquid phase separation of proteins have been broadly observed in many cellular machineries, but the biological roles of many of these protein condensates remains ambiguous. Condensates of the membrane protein LAT with Grb2+Sos1 have been implicated in T cell activation, possibly by excluding inhibitory phosphatase CD45 through electrostatic repulsion and/or increasing the dwell time of effector protein Sos1 near the plasma membrane (PM). Intriguingly, LAT has been widely shown to reside in ordered PM domains known as lipid rafts.