Local translation in microglial processes is required for efficient phagocytosis

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Neurons, astrocytes, and oligodendrocytes regulate protein translation in their distal processes.
• The role of local translation in microglial processes, particularly peripheral microglial processes (PeMPs), remains largely unexplored.

Purpose of the Study:

• To investigate whether regulated local protein translation occurs within peripheral microglial processes (PeMPs) in the mouse brain.
• To determine the functional significance of local translation in PeMPs for microglial activities.

Main Methods:

• Analysis of ribosome engagement and associated transcripts in PeMPs.
• Live slice preparation to assess the impact of translation blockade on PeMP function.
• Observation of PeMP behavior and phagocytosis in response to severed conditions and translation inhibition.

Main Results:

• PeMPs contain active ribosomes involved in de novo protein synthesis, associated with transcripts for pathogen defense, motility, and phagocytosis.
• Inhibition of acute translation in PeMPs impaired phagocytic cup formation, lysosomal protein localization, and the phagocytosis of apoptotic cells and pathogen-like particles.
• Severed PeMPs demonstrated and required de novo local protein synthesis for effective phagocytosis of pathogen-like particles.

Conclusions:

• These findings provide evidence for regulated local protein translation within peripheral microglial processes.
• Local protein synthesis in PeMPs is crucial for supporting dynamic microglial functions, including phagocytosis and response to pathogens.