Jingru Wang, Juan Xiong, Shuhan Zhang, Dongchen Li, Qingzhu Chu, Weiping Chang, Lin Deng, Wei-Ke Ji
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引用次数: 0
摘要
早期内体(EE)在囊泡运输的货物分拣过程中至关重要。用于降解的货物被保留在 EEs 中并最终运输到溶酶体,而用于质膜(PM)或高尔基体的回收货物则在货物分拣过程中被分离到被称为 EE 芽的特化膜结构中。尽管意义重大,但人们对 EE 芽形成过程中膜扩张的分子基础知之甚少。在这项研究中,我们发现了一个由 SHIP164、ATP 酶 RhoBTB3 和 retromer 亚基 Vps26B 组成的蛋白复合物,它能促进 EE 芽在高尔基-EE 接触点的形成。我们的研究结果表明,Vps26B 是一种新型的 Rab14 效应器,Rab14 活性调节 SHIP164 与 EE 的结合。耗尽 SHIP164 会导致 Rab14+ EEs 变大而无芽,野生型 SHIP164 能挽救这种表型,而脂质转移缺陷突变体则不能。RhoBTB3 或 Vps26B 的抑制反映了 SHIP164 缺失的效果。综上所述,我们提出了一种由 RhoBTB3-SHIP164-Vps26B 复合物在高尔基-EE 接触点介导的脂质转运依赖性途径,它对 EE 的出芽至关重要。
Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex
Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi–EE contacts. Our findings reveal that Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 leads to enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not the lipid transfer-defective mutants. Suppression of RhoBTB3 or Vps26B mirrors the effects of SHIP164 depletion. Together, we propose a lipid transport-dependent pathway mediated by the RhoBTB3–SHIP164–Vps26B complex at Golgi–EE contacts, which is essential for EE budding.
Cell DiscoveryBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍:
Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research.
Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals.
In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.