ABSTRACT

Macroautophagy/autophagy refers to the engulfment of cellular contents selected for lysosomal degradation. The final step in autophagy is the fusion of autophagosome with the lysosome, which is mediated by SNARE proteins. Of the SNAREs, autophagosome-localized Q-SNAREs, such as STX17 and SNAP29, and lysosome-localized R-SNAREs, such as VAMP8 or VAMP7, have been reported to be involved. Recent studies also reveal participation of the R-SNARE, YKT6, in autophagosome-lysosome fusion. These SNAREs, with the help of other regulatory factors, act coordinately to spatiotemporally control the fusion process. Besides regulating autophagosome-lysosome fusion, some SNAREs, such as STX17, also function in other autophagic processes, including autophagosome formation and mitophagy. A better understanding of the functions of SNAREs will shed light on the molecular mechanisms of autophagosome-lysosome fusion as well as on the mechanisms by which autophagy is globally regulated.

Abbreviations: ATG: autophagy related; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; IRGM: immunity related GTPase M; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PLEKHM1: pleckstrin homology and RUN domain containing M1; PRKN: PRKN RBR E3 ubiquitin protein ligase; RAB2A: RAB2A, member RAS oncogene family; RAB33B: RAB33B, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; RB1CC1: RB1 inducible coiled-coil 1; RTN3: reticulon 3; RUBCNL: rubicon like autophagy enhancer; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNAP29: synaptosomal associated protein 29; STX17: syntaxin 17; ULK1: unc-51 like autophagy activating kinase 1; VAMP7: vesicle associated membrane protein 7; VAMP8: vesicle associated membrane protein 8; YKT6: YKT6 v-SNARE homolog

摘要

巨自噬/自噬是指吞噬选择用于溶酶体降解的细胞内容物。自噬的最后一步是自噬体与溶酶体的融合，这是由 SNARE 蛋白介导的。据报道，在 SNARE 中，自噬体定位的 Q-SNARE（例如 STX17 和 SNAP29）和溶酶体定位的 R-SNARE（例如 VAMP8 或 VAMP7）参与其中。最近的研究还揭示了 R-SNARE、YKT6 参与自噬体-溶酶体融合。这些 SNARE 在其他调节因素的帮助下协调作用，以时空控制融合过程。除了调节自噬体-溶酶体融合外，一些 SNARE（例如 STX17）还在其他自噬过程中发挥作用，包括自噬体形成和线粒体自噬。更好地了解 SNARE 的功能将有助于阐明自噬体-溶酶体融合的分子机制以及自噬全局调节的机制。

缩写：ATG：自噬相关；DNM1L：动力1样；ER：内质网；GABARAP：GABA A 型受体相关蛋白；GABARAPL1：GABA A 型受体相关蛋白样 1；IRGM：免疫相关GTPase M；LAMP2：溶酶体相关膜蛋白2；MAP1LC3B/LC3：微管相关蛋白1轻链3β；MTOR：雷帕霉素激酶的机制靶点；PIK3R4：磷酸肌醇-3-激酶调节亚基4；PLEKHM1：pleckstrin同源性和含有M1的RUN结构域；PRKN：PRKN RBR E3 泛素蛋白连接酶；RAB2A：RAB2A，RAS癌基因家族成员；RAB33B：RAB33B，RAS癌基因家族成员；RAB7A：RAB7A，RAS癌基因家族成员；RB1CC1：RB1感应线圈1；RTN3：网状结构3；RUBCNL：rubicon样自噬增强剂；SNARE：可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体；SNAP29：突触体相关蛋白29；STX17: 语法蛋白 17; ULK1：unc-51 样自噬激活激酶 1；VAMP7：囊泡相关膜蛋白7；VAMP8：囊泡相关膜蛋白8；YKT6：YKT6 v-SNARE 同系物