α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles
文献类型：期刊论文
| 作者 | Li, Qun1,3,4; Hu, Tao4; Li, Fan4; Xing, Yutong2,3,4; Wu, Zhenyong1,2,3,4 |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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| 出版日期 | 2025-08-20 |
| 卷号 | 147期号:33页码:29829-29837 |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/jacs.5c06021 |
| 通讯作者 | Wu, Zhenyong(wuzhenyong@simm.ac.cn) |
| 英文摘要 | alpha-Synuclein (alpha-syn) disrupts synaptic vesicle architecture in Parkinson's disease (PD), yet the underlying mechanisms remain unclear. Here, we identify a previously unrecognized phenomenon in which alpha-syn (>= 20 mu M) rapidly induces SNARE-dependent tubular protrusions on highly curved small unilamellar vesicles (similar to 45 nm in diameter). This process requires functional v- and t-SNAREs, as neither v-SNARE nor t-SNARE alone, nor predocked SNARE complexes or CDV-treated SNARE liposomes, support tubulation. Notably, the familial PD-associated mutations A30P and E46K enhance tubule formation, whereas A53T exhibits minimal activity. Disrupting the alpha-syn-VAMP2 interaction abolishes tubulation, directly linking this interface to vesicle remodeling. Tubule formation increases with alpha-syn concentration, impairs SNARE-mediated membrane fusion, and significantly modulates alpha-syn liquid-liquid phase separation (LLPS), underscoring its pathological relevance. These findings reveal a novel mechanism by which alpha-syn remodels vesicle architecture, providing deeper insights into synaptic dysfunction in PD. |
| WOS关键词 | MEMBRANE INTERACTIONS ; SYNPHILIN-1 ; PARKINSON |
| 资助项目 | Key R&D Program of Shandong Province, China[2024CXPT029] ; National Natural Science Foundation of China[32371283] ; Taishan Scholars Program[2023000027] ; Special Supporting Funds for Leading Talents at or Above the Provincial Level in Yantai City[2023000090] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001545746700001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321216]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Zhenyong |
| 作者单位 | 1.Yantai Univ, Sch Pharm, Key Lab Mol Pharmacol & Drug Evaluat, Minist Educ, Yantai 264005, Shandong, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Qun,Hu, Tao,Li, Fan,et al. α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025,147(33):29829-29837. |
| APA | Li, Qun,Hu, Tao,Li, Fan,Xing, Yutong,&Wu, Zhenyong.(2025).α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,147(33),29829-29837. |
| MLA | Li, Qun,et al."α-Synuclein Drives SNARE-Dependent Tubular Remodeling of Vesicles".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147.33(2025):29829-29837. |
入库方式： OAI收割
来源：上海药物研究所
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