UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis

Phagocytosis is thought to be initiated by activation of phagocytosis-promoting receptors that recognize 'eat-me' signals such as phosphatidylserine or amyloid-β expressed in the apoptotic cells. But now Koizumi et al. demonstrate a novel type of microglial phagocytosis that requires neither typical 'eat-me' signals nor Fc receptor ligands for initiation. Instead, this phagocytosis is promoted by the diffusible extracellular molecule uridine 5′-diphosphate, released by injured cells. The UDP activates P2Y6 receptors on the microglial surface. The clearance of dead cells is crucial to the maintenance of brain function, so these findings may have implications for a range of central nervous system diseases.