ABSTRACT

Macroautophagy is a highly conserved eukaryotic cellular pathway involving the engulfment of macromolecules, organelles, and invading microbes by a double-membrane compartment and subsequent lysosomal degradation. The mechanisms that regulate macroautophagy, and the interaction of its components with other cellular pathways, have remained unclear. Here, we performed proximity-dependent biotin identification (BioID) on 39 core human macroautophagy proteins, identifying over 700 unique high confidence proximity interactors with new putative connections between macroautophagic and essential cellular processes. Of note, we identify members of the OSBPL (oxysterol binding protein like) family as Atg8-family protein interactors. We subsequently conducted comprehensive screens of the OSBPL family for LC3B-binding and roles in xenophagy and aggrephagy. OSBPL7 and OSBPL11 emerged as novel lipid transfer proteins required for macroautophagy of selective cargo. Altogether, our proximity interaction map provides a valuable resource for the study of autophagy and highlights the critical role of membrane contact site proteins in the pathway.

Abbreviations

BioID: proximity-dependent biotin identification; GO: gene ontology; OSBPL: oxysterol binding protein like; VAPA: VAMP associated protein A; VAPB: VAMP associated protein B and C

中文翻译：

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人类巨自噬途径的全球邻近相互作用组

摘要

巨自噬是一种高度保守的真核细胞通路，涉及通过双膜隔室吞噬大分子、细胞器和入侵微生物以及随后的溶酶体降解。调节巨自噬的机制及其成分与其他细胞通路的相互作用仍不清楚。在这里，我们对 39 种核心人类巨自噬蛋白进行了接近依赖性生物素鉴定 (BioID)，鉴定了 700 多种独特的高可信度接近相互作用因子，这些相互作用因子在巨自噬和基本细胞过程之间具有新的推定联系。值得注意的是，我们将 OSBPL（类氧固醇结合蛋白）家族的成员鉴定为 Atg8 家族蛋白相互作用体。我们随后对 OSBPL 家族进行了全面筛选，以了解 LC3B 结合以及在异种吞噬和聚集吞噬中的作用。OSBPL7 和 OSBPL11 成为选择性货物巨自噬所需的新型脂质转移蛋白。总而言之，我们的邻近相互作用图为自噬研究提供了宝贵的资源，并突出了膜接触位点蛋白在该途径中的关键作用。

缩略语

BioID：接近依赖性生物素识别；GO：基因本体；OSBPL：氧固醇结合蛋白样；VAPA：VAMP 相关蛋白 A；VAPB：VAMP 相关蛋白 B 和 C