Membrane scission driven by the PROPPIN Atg18
Membrane scission driven by the PROPPIN Atg18
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DOI：
10.15252/embj.201796859
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发表时间：
2017-11-15
期刊：
影响因子：
11.4
通讯作者：
Mayer, Andreas
中科院分区：
文献类型：
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作者：
Gopaldass, Navin;Fauvet, Bruno;Mayer, Andreas
内体和溶酶体中蛋白质的分选、转运和自噬降解以及这些细胞器的分裂依赖于膜结合的管泡载体的断裂。断裂是如何发生的知之甚少，但家族蛋白结合这些膜。在这里，我们表明，酵母PROPPIN Atg18进行膜断裂活性。纯化的Atg18驱动巨大单层囊泡的破裂和断裂。在膜接触时，Atg18将其非结构化CD环折叠成插入双层的两亲性α-螺旋。这允许蛋白质与PI3P和PI（3，5）P2的两个脂质结合位点结合。PI（3，5）P2诱导Atg18寡聚化，其应将脂质插入的α-螺旋集中在外膜小叶中并驱动膜微管化和断裂。Atg18的断裂活性与其在内-溶酶体蛋白运输、自噬体生物发生和空泡分裂中的已知作用相容。Atg18的膜断裂和断裂所需的关键特征是由其他PROPPIN共享的，这表明膜断裂可能是该蛋白质家族的通用功能。
Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family proteins bind these membranes. Here, we show that the yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives tubulation and scission of giant unilamellar vesicles. Upon membrane contact, Atg18 folds its unstructured CD loop into an amphipathic alpha-helix that inserts into the bilayer. This allows the protein to engage its two lipid binding sites for PI3P and PI(3,5)P2. PI(3,5) P2 induces Atg18 oligomerization, which should concentrate lipid-inserted alpha-helices in the outer membrane leaflet and drive membrane tubulation and scission. The scission activity of Atg18 is compatible with its known roles in endo-lysosomal protein trafficking, autophagosome biogenesis, and vacuole fission. Key features required for membrane tubulation and scission by Atg18 are shared by other PROPPINs, suggesting that membrane scission may be a generic function of this protein family.