mTOR regulates phagosome and entotic vacuole fission.
mTOR regulates phagosome and entotic vacuole fission.
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DOI：
10.1091/mbc.e13-07-0408
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发表时间：
2013-12
影响因子：
3.3
通讯作者：
Overholtzer M
中科院分区：
文献类型：
--
作者：
Krajcovic M;Krishna S;Akkari L;Joyce JA;Overholtzer M
吞噬体和容纳吞噬细胞的内泡经历mTOR调节的空泡分裂过程，其将吞噬的内容物分布在整个溶酶体网络中。从吞噬细胞中回收氨基酸激活mTORC 1，并将吞噬细胞从氨基酸饥饿的影响中拯救出来。由吞噬作用或活细胞吞噬程序内吞形成的巨内吞空泡经历连续的成熟步骤，导致消化内化的货物的溶酶体融合。货物消化后，营养物质必须输出到胞质溶胶，和液泡膜必须处理的机制，仍然不清楚。在这里，我们发现，吞噬体和内吞空泡经历了一个后期成熟的步骤，其特征在于分裂，重新分配空泡内容物进入溶酶体网络。雷帕霉素分裂受丝氨酸/苏氨酸蛋白激酶哺乳动物雷帕霉素靶蛋白复合物1（mTORC 1）的调节，mTORC 1定位于吞噬细胞周围的液泡膜。降解的吞噬细胞为吞噬细胞提供用于翻译的氨基酸，并在饥饿的巨噬细胞和肿瘤细胞中拯救细胞存活和mTORC 1活性。这些数据确定了吞噬和内吞的晚期阶段，其涉及通过mTOR调节的膜分裂处理大空泡。
Phagosomes and entotic vacuoles harboring engulfed cells undergo an mTOR-regulated process of vacuolar fission that distributes engulfed contents throughout lysosome networks. Amino acid recovery from engulfed cells activates mTORC1 and rescues engulfing cells from the effects of amino acid starvation. Macroendocytic vacuoles formed by phagocytosis, or the live-cell engulfment program entosis, undergo sequential steps of maturation, leading to the fusion of lysosomes that digest internalized cargo. After cargo digestion, nutrients must be exported to the cytosol, and vacuole membranes must be processed by mechanisms that remain poorly defined. Here we find that phagosomes and entotic vacuoles undergo a late maturation step characterized by fission, which redistributes vacuolar contents into lysosomal networks. Vacuole fission is regulated by the serine/threonine protein kinase mammalian target of rapamycin complex 1 (mTORC1), which localizes to vacuole membranes surrounding engulfed cells. Degrading engulfed cells supply engulfing cells with amino acids that are used in translation, and rescue cell survival and mTORC1 activity in starved macrophages and tumor cells. These data identify a late stage of phagocytosis and entosis that involves processing of large vacuoles by mTOR-regulated membrane fission.