Microglial microvesicle secretion and intercellular signaling

Microvesicles (MVs) are released from almost all cell brain types into the microenvironment and are emerging as a novel way of cell-to-cell communication. This review focuses on MVs discharged by microglial cells, the brain resident myeloid cells, which comprise similar to 10-12% of brain population. We summarize first evidence indicating that MV shedding is a process activated by the ATP receptor P2X(7) and that shed MVs represent a secretory pathway for the inflammatory cytokine IL-beta. We then discuss subsequent findings which clarify how IL-beta can be locally processed and released from MVs into the extracellular environment. In addition, we describe the current understanding about the mechanism of P2X(7)-dependent MV formation and membrane abscission, which, by involving sphingomyelinase activity and ceramide formation, may share similarities with exosome biogenesis. Finally we report our recent results which show that microglia-derived MVs can stimulate neuronal activity and participate to the propagation of inflammatory signals, and suggest new areas for future investigation.