Autophagy genes coordinate with the class II PI/PtdIns 3-kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans
Autophagy genes coordinate with the class II PI/PtdIns 3-kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans
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DOI：
10.4161/auto.26323
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发表时间：
2013-12-01
期刊：
影响因子：
13.3
通讯作者：
Wang, Xiaochen
中科院分区：
文献类型：
--
作者：
Cheng, Shiya;Wu, Yanwei;Wang, Xiaochen
吞噬作用和自噬作用是两种溶酶体介导的细胞降解途径，旨在消除细胞外和细胞内成分，分别。最近的研究表明，这两个过程相互交叉。一些自噬蛋白已被证明参与凋亡细胞的清除，但自噬途径是否以及如何参与尚不清楚。在此，我们发现，在自噬的重叠或不同阶段作用的19个基因的功能缺失突变导致了C.线虫胚胎相反，通过自噬介导P颗粒或蛋白质聚集体的特异性清除的基因对于细胞尸体的去除是无意义的。我们发现，有缺陷的自噬损害吞噬体的成熟，自噬基因的作用平行于II类磷脂酰肌醇（PI）/磷脂酰肌醇（PtdIns）3-激酶PIKI-1调节吞噬体PtdIns 3 P在一个类似的方式作为VPS-34。我们的数据表明，自噬可能与PIKI-1协调，以促进吞噬体成熟，从而确保有效清除凋亡细胞。
Phagocytosis and autophagy are two lysosome-mediated cellular degradation pathways designed to eliminate extracellular and intracellular constituents, respectively. Recent studies suggest that these two processes intersect. Several autophagy proteins have been shown to participate in clearance of apoptotic cells, but whether and how the autophagy pathway is involved is unclear. Here we showed that loss of function mutations in 19 genes acting at overlapping or distinct stages of autophagy caused increased numbers of cell corpses in C. elegans embryos. In contrast, genes that mediate specific clearance of P granules or protein aggregates through autophagy are dispensable for cell corpse removal. We showed that defective autophagy impairs phagosome maturation and that autophagy genes act in parallel to the class II phosphoinositide (PI)/phosphatidylinositol (PtdIns) 3-kinase PIKI-1 to regulate phagosomal PtdIns3P in a similar manner as VPS-34. Our data indicate that autophagy may coordinate with PIKI-1 to promote phagosome maturation, thus ensuring efficient clearance of apoptotic cells.