Local translation in microglial processes is required for efficient phagocytosis

• Published in: Nature neuroscience Vol. 26; no. 7; pp. 1185 - 1195
• Main Authors: Vasek, Michael J., Mueller, Shayna M., Fass, Stuart B., Deajon-Jackson, Jelani D., Liu, Yating, Crosby, Haley W., Koester, Sarah K., Yi, Jiwon, Li, Qingyun, Dougherty, Joseph D.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2023; Nature Publishing Group
• Subjects: 13; 13/51; 14; 14/19; 14/32; 38; 38/91; 631/250/371; 631/378/2596/1953; 631/378/87; Animal Genetics and Genomics; Animals; Apoptosis; Astrocytes; Astrocytes - metabolism; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain slice preparation; Localization; Mice; Microglia; Microglia - metabolism; Neurobiology; Neurons - metabolism; Neurosciences; Oligodendrocytes; Pathogens; Phagocytes; Phagocytosis; Phagocytosis - physiology; Protein biosynthesis; Protein synthesis; Proteins; Ribosomes; Translation; Translations
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-023-01353-0

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. 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.