The Rag-Ragulator Complex Regulates Lysosome Function and Phagocytic Flux in Microglia.
The Rag-Ragulator Complex Regulates Lysosome Function and Phagocytic Flux in Microglia.
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DOI：
10.1016/j.celrep.2015.12.055
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发表时间：
2016-01-26
期刊：
影响因子：
8.8
通讯作者：
Talbot WS
中科院分区：
文献类型：
--
作者：
Shen K;Sidik H;Talbot WS
小胶质细胞是CNS的常驻巨噬细胞，其对于在发育期间吞噬凋亡神经元和弱突触是必需的。我们发现，RagA和Lamtor 4，Rag-Ragulator复合物的两个组成部分，是小胶质细胞中溶酶体的重要调节因子。在缺乏RagA功能的斑马鱼中，小胶质细胞表现出扩大的溶酶体区室，但不能正确消化凋亡的神经元碎片。以前的生化研究已经将Rag-Ragulator复合物置于mTORC 1激活的上游，以响应细胞营养物质的可用性。尽管如此，RagA和mTOR突变体斑马鱼具有不同的表型，表明Rag-Ragulator复合物具有独立于mTOR信号传导的功能。我们的分析揭示了Rag-Ragulator复合物在小胶质细胞中适当的溶酶体功能和吞噬流量中的重要作用。
Microglia are resident macrophages of the CNS that are essential for phagocytosis of apoptotic neurons and weak synapses during development. We show that RagA and Lamtor4, two components of the Rag-Ragulator complex, are essential regulators of lysosomes in microglia. In zebrafish lacking RagA function, microglia exhibit an expanded lysosomal compartment but are unable to properly digest apoptotic neuronal debris. Previous biochemical studies have placed the Rag-Ragulator complex upstream of mTORC1 activation in response to cellular nutrient availability. Nonetheless, RagA and mTOR mutant zebrafish have distinct phenotypes, indicating that the Rag-Ragulator complex has functions independent of mTOR signaling. Our analysis reveals an essential role of the Rag-Ragulator complex in proper lysosome function and phagocytic flux in microglia.