华中科技大学Yueguang Rong和Cong Ma共同合作，近期取得重要工作进展。他们研究提出，STX17-SNAP47-VAMP7/VAMP8复合体是介导自噬体-溶酶体融合的默认SNARE复合体。相关研究成果2024年1月5日在线发表于《细胞研究》杂志上。

据介绍，SNARE复合物介导的自噬体-溶酶体融合是自噬的重要步骤。两种含有SNAP29的SNARE复合物在饥饿诱导的大量自噬中已被广泛研究，而在非饥饿条件下发生的其它类型自噬中相关的SNARE复合体却被忽视了。

研究人员发现，在非饥饿条件下选择性自噬的自噬体-溶酶体融合不需要含有SNAP29的SNARE复合物，而是需要STX17-SNAP47-VAMP7/VAMP8 SNARE复合物。

此外，STX17-SNAP47-VAMP7/VAMP8 SNARE复合物也在饥饿诱导的自噬中发挥作用。SNAP47通过其Pleckstring同源结构域同时检测到ATG8s和PI（4，5）P₂后被募集到自噬体。相反，在非饥饿条件下，由于O-GlcNAcylation的失活，含有SNAP29的SNARE被排除在选择性自噬之外。

总之，这些发现描述了一种以前未知的默认SNARE复合物，负责选择性和大量自噬中的自噬体-溶酶体融合，这可以指导自噬相关疾病的研究和治疗方法开发。

附：英文原文

Title: The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome–lysosome fusion

Author: Jian, Fenglei, Wang, Shen, Tian, Rui, Wang, Yufen, Li, Chuangpeng, Li, Yan, Wang, Shixuan, Fang, Chao, Ma, Cong, Rong, Yueguang

Issue&Volume: 2024-01-05

Abstract: Autophagosome–lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome–lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome–lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.

DOI: 10.1038/s41422-023-00916-x

Source: https://www.nature.com/articles/s41422-023-00916-x