Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex
Abstract 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 struc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-04-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00651-6 |
| _version_ | 1797220034778497024 |
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| author | Jingru Wang Juan Xiong Shuhan Zhang Dongchen Li Qingzhu Chu Weiping Chang Lin Deng Wei-Ke Ji |
| author_facet | Jingru Wang Juan Xiong Shuhan Zhang Dongchen Li Qingzhu Chu Weiping Chang Lin Deng Wei-Ke Ji |
| author_sort | Jingru Wang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T12:43:08Z |
| format | Article |
| id | doaj.art-e890f97f05a1422b86871094ff8fb177 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-24T12:43:08Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-e890f97f05a1422b86871094ff8fb1772024-04-07T11:08:09ZengNature Publishing GroupCell Discovery2056-59682024-04-0110112010.1038/s41421-024-00651-6Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complexJingru Wang0Juan Xiong1Shuhan Zhang2Dongchen Li3Qingzhu Chu4Weiping Chang5Lin Deng6Wei-Ke Ji7Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and TechnologyDepartment of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and TechnologyShenzhen Bay LaboratoryShenzhen Bay LaboratoryDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41421-024-00651-6 |
| spellingShingle | Jingru Wang Juan Xiong Shuhan Zhang Dongchen Li Qingzhu Chu Weiping Chang Lin Deng Wei-Ke Ji Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex Cell Discovery |
| title | Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex |
| title_full | Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex |
| title_fullStr | Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex |
| title_full_unstemmed | Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex |
| title_short | Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex |
| title_sort | biogenesis of rab14 positive endosome buds at golgi endosome contacts by the rhobtb3 ship164 vps26b complex |
| url | https://doi.org/10.1038/s41421-024-00651-6 |
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