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ShanghaiTech University Knowledge Management System
| Axon Trafficking Counteracts Aberrant Protein Aggregation in Neurons | |
| 2025-01-17 | |
| 状态 | 已发表 |
| 摘要 | Directed axon trafficking of mRNA via ribonucleoprotein complexes (RNPs) is essential for the proper function and survival of neurons. However, the mechanisms governing RNP transport in axons remain poorly understood. Here, we identify Annexin A7 (ANXA7) as a critical adaptor facilitating the retrograde transport of T-cell intracellular antigen 1 (TIA1)-containing RNPs by linking them to the cytoplasmic dynein. Persistent axonal Ca2+ elevation disrupts ANXA7's linker role, causing the detachment of TIA1 granules from dynein, consequently impairing transport and triggering pathological TIA1 aggregation within axons. Similarly, ANXA7 knockdown decouples TIA1 granules from dynein, severely obstructing trafficking and causing pathological aggregation of TIA1 in axons, which culminates in axonopathy and neurodegeneration both in vitro and in vivo. Conversely, ANXA7 overexpression enhances trafficking and counteracts aberrant aggregation of TIA1-containing RNPs in axons. Our findings elucidate a novel mechanism underlying RNP axonal transport, highlighting its significance in the biology and pathology of central neurons. |
| 语种 | 英语 |
| DOI | 10.1101/2025.01.16.633295 |
| 相关网址 | 查看原文 |
| 出处 | bioRxiv |
| 收录类别 | PPRN.PPRN |
| WOS记录号 | PPRN:120810677 |
| WOS类目 | Neurosciences |
| 资助项目 | Double First-Class Initiative Fund of ShanghaiTech University["SYLPOC0022022","SYLDX0302022"] ; National Natural Science Foundation of China["32271001","31871036","32100777"] |
| 文献类型 | 预印本 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/503600 |
| 专题 | 生命科学与技术学院 物质科学与技术学院 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 物质科学与技术学院_博士生 生命科学与技术学院_本科生 生命科学与技术学院_PI研究组_王彤组 |
| 通讯作者 | Wang, Tong |
| 作者单位 | 1.Shanghaitech Univ, Ctr Brain Sci, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Phys Sci & Technol, Div Chem & Phys Biol, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Yu,Luan, Tongshu,Zhang, Zhenda,et al. Axon Trafficking Counteracts Aberrant Protein Aggregation in Neurons. 2025. |
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