An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins
An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins
复制标题
内质网 ATP 酶通过去除异位定位的线粒体蛋白来保护内质网身份
DOI：
10.1016/j.celrep.2020.108363
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发表时间：
2020-11-10
期刊：
影响因子：
8.8
通讯作者：
Wang, Xiangming
中科院分区：
文献类型：
--
作者：
Qin, Qing;Zhao, Ting;Wang, Xiangming
膜蛋白严格靶向相应的细胞器对细胞器的身份和功能至关重要。除了将蛋白质靶向到适当细胞器的分子途径外，监视机制还可以从不需要的目的地清除错误靶向的蛋白质。虽然Msp1在线粒体膜上起去除错靶蛋白的作用，但内质网（ER）的监视机制尚不清楚。在这里，我们展示了一个定位于内质网的保守的p5a型atp酶CATP-8，从内质网去除异位线粒体尾锚定（TA）和信号锚定（SA）蛋白。在catp-8突变体中，线粒体裂变蛋白fis1错定位于内质网膜。与另一种线粒体裂变蛋白MFF-2一起，fis1以动力蛋白相关蛋白（DRP-1）依赖的方式引起内质网断裂。此外，CATP-8对树突的发育至关重要。cap -8突变体显著降低了树突引导受体DMA-1的水平，导致树突乔木减少。因此，P5A atp酶通过防止线粒体蛋白错定位来保护内质网形态和功能。
Stringent targeting of membrane proteins to corresponding organelles is essential for organelle identity and functions. In addition to molecular pathways that target proteins to appropriate organelles, surveillance mechanisms clear mistargeted proteins from undesired destinations. Although Msp1 functions on the mitochondrial membrane to remove mistargeted proteins, the surveillance mechanism for the endoplasmic reticulum (ER) is not well understood. Here, we show that a conserved P5A-type ATPase CATP-8, which localizes to ER, removes ectopic mitochondrial tail-anchored (TA) and signal-anchored (SA) proteins from the ER. In catp-8 mutant, mitochondria fission protein FIS-1 mislocalizes to the ER membrane. Together with another mitochondria fission protein MFF-2, FIS-1 causes ER fragmentation in a Dynamin-related protein (DRP-1)-dependent manner. In addition, CATP-8 is essential for dendrite development. catp-8 mutant dramatically reduces the level of the dendrite guidance receptor DMA-1, leading to diminished dendritic arbors. Hence, P5A ATPase safeguards ER morphology and functions by preventing mitochondrial proteins mislocalization.