Gyp1 has a dual function as Ypt1 GAP and interaction partner of Atg8 in selective autophagy
Gyp1 has a dual function as Ypt1 GAP and interaction partner of Atg8 in selective autophagy
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DOI：
10.1080/15548627.2019.1569929
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发表时间：
2019-06-03
期刊：
影响因子：
13.3
通讯作者：
Krick, Roswitha
中科院分区：
文献类型：
--
作者：
Mitter, Anne Lisa;Schlotterhose, Petra;Krick, Roswitha
巨自噬/自噬是一种高度保守的细胞内囊泡运输途径，可防止细胞内有害物质的积累。不同自噬蛋白复合物在所谓的噬菌体组装位点 (PAS) 的动态组装和分解受到严格调控。 Rab GTPase 是细胞囊泡运输的主要调节因子，Rab GTPase Ypt1 及其 GEF TRAPPIII 与自噬有关。我们表明，Gyp1 作为 Ypt1 GTP 酶激活蛋白 (GAP)，用于选择性自噬变异，例如 Cvt 途径或线粒体的选择性自噬降解（线粒体自噬）。 Gyp1 调节保守 Ypt1-Atg1 复合物的动态分解。因此，Gyp1 为 Atg14 的有效招募奠定了基础，并促进了噬菌体从成核到伸长的关键步骤。此外，我们还发现 Gyp1 是一种新的 Atg8 相互作用基序 (AIM) 依赖的 Atg8 相互作用伴侣。 Gyp1 AIM 是有效形成货物受体-Atg8 复合物所必需的。我们的研究结果阐明了吞噬泡形成过程中复杂分解的分子机制，并表明了 GAP 在细胞囊泡运输中的潜在双重功能。 Atg，自噬相关； Cvt，细胞质到液泡的靶向； GAP、GTP酶激活蛋白； GEF，鸟嘌呤核苷酸交换因子； GFP，绿色荧光蛋白；对数生长期，对数生长期； NHD，N-末端螺旋结构域； PAS，吞噬细胞组装位点； PE、磷脂酰乙醇胺； PtdIns3P，磷脂酰肌醇-3-磷酸； WT，野生型
Macroautophagy/autophagy is a highly conserved intracellular vesicle transport pathway that prevents accumulation of harmful materials within cells. The dynamic assembly and disassembly of the different autophagic protein complexes at the so-called phagophore assembly site (PAS) is strictly regulated. Rab GTPases are major regulators of cellular vesicle trafficking, and the Rab GTPase Ypt1 and its GEF TRAPPIII have been implicated in autophagy. We show that Gyp1 acts as a Ypt1 GTPase-activating protein (GAP) for selective autophagic variants, such as the Cvt pathway or the selective autophagic degradation of mitochondria (mitophagy). Gyp1 regulates the dynamic disassembly of the conserved Ypt1-Atg1 complex. Thereby, Gyp1 sets the stage for efficient Atg14 recruitment, and facilitates the critical step from nucleation to elongation of the phagophore. In addition, we identified Gyp1 as a new Atg8-interacting motif (AIM)-dependent Atg8 interaction partner. The Gyp1 AIM is required for efficient formation of the cargo receptor-Atg8 complexes. Our findings elucidate the molecular mechanisms of complex disassembly during phagophore formation and suggest potential dual functions of GAPs in cellular vesicle trafficking.Abbreviations AIM, Atg8-interacting motif; Atg, autophagy related; Cvt, cytoplasm-to-vacuole targeting; GAP, GTPase-activating protein; GEF, guanine-nucleotide exchange factor; GFP, green fluorescent protein; log phase, logarithmic growth phase; NHD, N-terminal helical domain; PAS, phagophore assembly site; PE, phosphatidylethanolamine; PtdIns3P, phosphatidylinositol-3-phosphate; WT, wild-type