Institute of Biomedical Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, China.
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China.
Autophagy. 2021 Oct;17(10):2680-2688. doi: 10.1080/15548627.2020.1823124. Epub 2020 Sep 24.
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.: 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.
自噬是指细胞内容物被溶酶体降解的过程。自噬的最后一步是自噬体与溶酶体融合,这一过程由 SNARE 蛋白介导。在 SNARE 中,已经报道自噬体定位的 Q-SNAREs,如 STX17 和 SNAP29,以及溶酶体定位的 R-SNAREs,如 VAMP8 或 VAMP7,参与了这一过程。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 蛋白在其他调节因子的帮助下,协调作用以时空方式控制融合过程。除了调节自噬体-溶酶体融合外,一些 SNARE 蛋白,如 STX17,还参与其他自噬过程,包括自噬体形成和线粒体自噬。更好地了解 SNARE 蛋白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的全局调控机制。: ATG: 自噬相关; DNM1L: 动力蛋白 1 样; ER: 内质网; GABARAP: GABA 型 A 受体相关蛋白; GABARAPL1: GABA 型 A 受体相关蛋白样 1; IRGM: 免疫相关 GTP 酶 M; LAMP2: 溶酶体相关膜蛋白 2; MAP1LC3B/LC3: 微管相关蛋白 1 轻链 3β; MTOR: 雷帕霉素靶蛋白激酶; PIK3R4: 磷酸肌醇 3-激酶调节亚基 4; PLEKHM1: pleckstrin 同源和 RUN 结构域包含 M1; 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 诱导卷曲螺旋 1; RTN3: 网质蛋白 3; RUBCNL: rubicon 样自噬增强子; SNARE: 可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体; SNAP29: 突触相关蛋白 29; STX17: 突触小泡相关蛋白 17; ULK1: 非典型卷曲螺旋激酶 1; VAMP7: 囊泡相关膜蛋白 7; VAMP8: 囊泡相关膜蛋白 8; YKT6: YKT6 v-SNARE 同源物。