Wang Jingru, Xiong Juan, Zhang Shuhan, Li Dongchen, Chu Qingzhu, Chang Weiping, Deng Lin, Ji Wei-Ke
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
Department of Ultrasound Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Cell Discov. 2024 Apr 2;10(1):38. doi: 10.1038/s41421-024-00651-6.
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.
早期内体（EEs）在囊泡运输中的货物分选过程中至关重要。虽然 destined for degradation 的货物会保留在早期内体中并最终转运至溶酶体，但 destined for the plasma membrane (PM) 或高尔基体的回收货物在货物分选过程中会被分隔到称为 EE 芽的特殊膜结构中。尽管具有这种重要性，但 EE 芽形成过程中膜扩张的分子基础仍知之甚少。在本研究中，我们鉴定出一种由SHIP164、一种ATP酶RhoBTB3和一种retromer亚基Vps26B组成的蛋白质复合物，该复合物在高尔基体 - EE接触位点促进EE芽的形成。我们的研究结果表明，Vps26B作为一种新的Rab14效应器发挥作用，并且Rab14活性调节SHIP164与早期内体的结合。SHIP164的缺失导致Rab14早期内体增大且无芽，野生型SHIP164可挽救该表型，但脂质转移缺陷型突变体则不能。RhoBTB3或Vps26B的抑制反映了SHIP164缺失的影响。我们共同提出了一条由RhoBTB3 - SHIP164 - Vps26B复合物在高尔基体 - EE接触位点介导的脂质运输依赖性途径，这对EE出芽至关重要。
