Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Neurosci. 2023 Jul;26(7):1185-1195. doi: 10.1038/s41593-023-01353-0. Epub 2023 Jun 5.
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.
神经元、星形胶质细胞和少突胶质细胞在远端突起内局部调节蛋白质翻译。在这里，我们测试了来自小鼠大脑的外周小胶质细胞突起（PeMP）内是否存在受调控的局部翻译。我们表明，PeMP 包含参与从头合成蛋白质的核糖体，这些核糖体与参与病原体防御、运动和吞噬作用的转录本相关。使用活体切片制备，我们进一步表明，急性翻译阻断会损害 PeMP 吞噬杯的形成、其中溶酶体蛋白的定位以及凋亡细胞和类病原体颗粒的吞噬作用。最后，与胞体分离的 PeMP 表现出并需要从头合成局部蛋白质，以有效地包围类病原体颗粒。总的来说，这些数据表明 PeMP 中存在受调控的局部翻译，并表明需要新的翻译来支持动态小胶质细胞功能。
