TY - JOUR
T1 - Local translation in microglial processes is required for efficient phagocytosis
AU - Vasek, Michael J.
AU - Mueller, Shayna M.
AU - Fass, Stuart B.
AU - Deajon-Jackson, Jelani D.
AU - Liu, Yating
AU - Crosby, Haley W.
AU - Koester, Sarah K.
AU - Yi, Jiwon
AU - Li, Qingyun
AU - Dougherty, Joseph D.
N1 - Funding Information:
We thank P. Bayguinov, G. Strout and the Washington University Center for Cellular Imaging for their expertise and training in live slice imaging and electron microscopy; K. Sakers for training and support; C. Weichselbaum for comments on the manuscript; and the Genome Technology Access Center (GTAC@MGI) for sequencing and library preparation. Funding was provided by 5R01NS102272 (to J.D.D.) and F32NS105363 (to M.V.), and a microgrant from the Washington University Center for Cellular Imaging. GTAC is partially supported by P30 CA91842 and UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Funding Information:
We thank P. Bayguinov, G. Strout and the Washington University Center for Cellular Imaging for their expertise and training in live slice imaging and electron microscopy; K. Sakers for training and support; C. Weichselbaum for comments on the manuscript; and the Genome Technology Access Center (GTAC@MGI) for sequencing and library preparation. Funding was provided by 5R01NS102272 (to J.D.D.) and F32NS105363 (to M.V.), and a microgrant from the Washington University Center for Cellular Imaging. GTAC is partially supported by P30 CA91842 and UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85160865840&partnerID=8YFLogxK
U2 - 10.1038/s41593-023-01353-0
DO - 10.1038/s41593-023-01353-0
M3 - Article
C2 - 37277487
AN - SCOPUS:85160865840
SN - 1097-6256
VL - 26
SP - 1185
EP - 1195
JO - Nature neuroscience
JF - Nature neuroscience
IS - 7
ER -