Local translation in microglial processes is required for efficient phagocytosis

Vasek et al. demonstrate that distal processes of microglia locally translate specific mRNAs including those related to immunity and phagocytosis. They then show that local protein synthesis is necessary for microglial process-initiated phagocytosis. Neurons, astrocytes and oligodendrocytes locally regulate protein translation within distal processes. Here, we tested whether there is regulated local translation within peripheral microglial processes (PeMPs) from mouse brain. We show that PeMPs contain ribosomes that engage in de novo protein synthesis, and these are associated with transcripts involved in pathogen defense, motility and phagocytosis. Using a live slice preparation, we further show that acute translation blockade impairs the formation of PeMP phagocytic cups, the localization of lysosomal proteins within them, and phagocytosis of apoptotic cells and pathogen-like particles. Finally, PeMPs severed from their somata exhibit and require de novo local protein synthesis to effectively surround pathogen-like particles. Collectively, these data argue for regulated local translation in PeMPs and indicate a need for new translation to support dynamic microglial functions.

Automated summary

Vasek et al. demonstrate that distal processes of microglia locally translate specific mRNAs related to immunity and phagocytosis. They show that local protein synthesis is necessary for microglial process-initiated phagocytosis. Neurons, astrocytes and oligodendrocytes also regulate protein translation within distal processes. Using a live slice preparation, they further show that acute translation blockade impairs the formation of peripheral microglial process (PeMP) phagocytic cups, lysosomal protein localization, and phagocytosis. These data suggest the importance of regulated local translation in PeMPs for dynamic microglial functions.