VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES–Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B–VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconventional cargo carrier that expedites ER-to-Golgi transport. In addition, depletion of VPS13B or Sec23IP delays ER export of procollagen, suggesting a link between procollagen secretion and joint laxity in patients with Cohen disease. Together, our study reveals a crucial role of VPS13B–Sec23IP interaction at the ERES–Golgi interface in the pathogenesis of Cohen syndrome.
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October 01 2024
Sec23IP recruits VPS13B/COH1 to ER exit site–Golgi interface for tubular ERGIC formation
Yuanjiao Du
,
Yuanjiao Du
*
(Conceptualization, Investigation, Methodology, Resources)
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
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Xinyu Fan
,
Xinyu Fan
*
(Data curation, Formal analysis, Investigation, Validation, Visualization)
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
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Chunyu Song
,
Chunyu Song
(Formal analysis)
3
Shenzhen Bay Laboratory
, Shenzhen, China
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Weiping Chang
,
Weiping Chang
(Funding acquisition, Resources)
3
Shenzhen Bay Laboratory
, Shenzhen, China
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Juan Xiong
,
Juan Xiong
(Data curation)
4Department of Anesthesiology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Lin Deng
,
Lin Deng
(Formal analysis, Funding acquisition, Investigation, Project administration, Resources)
3
Shenzhen Bay Laboratory
, Shenzhen, China
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Wei-Ke Ji
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
2
Cell Architecture Research Center, Huazhong University of Science and Technology
, Wuhan, China
3
Shenzhen Bay Laboratory
, Shenzhen, China
Correspondence to Wei-Ke Ji: [email protected]
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Yuanjiao Du
Conceptualization, Investigation, Methodology, Resources
*
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
Xinyu Fan
Data curation, Formal analysis, Investigation, Validation, Visualization
*
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
Chunyu Song
Formal analysis
3
Shenzhen Bay Laboratory
, Shenzhen, China
Weiping Chang
Funding acquisition, Resources
3
Shenzhen Bay Laboratory
, Shenzhen, China
Juan Xiong
Data curation
4Department of Anesthesiology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Lin Deng
Formal analysis, Funding acquisition, Investigation, Project administration, Resources
3
Shenzhen Bay Laboratory
, Shenzhen, China
Wei-Ke Ji
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
2
Cell Architecture Research Center, Huazhong University of Science and Technology
, Wuhan, China
3
Shenzhen Bay Laboratory
, Shenzhen, China
Correspondence to Wei-Ke Ji: [email protected]
*
Y. Du and X. Fan contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
February 13 2024
Revision Received:
June 25 2024
Accepted:
August 07 2024
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funder(s):
National Key R&D Program of China
- Award Id(s): 2022YFA1302800
Funder(s):
National Natural Science Foundation of China
- Award Id(s): 32270779,92354304,32371343,32122025,81901166
Funder(s):
Shenzhen Bay Scholars Program
© 2024 Du et al.
2024
Du et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2024) 223 (12): e202402083.
Article history
Received:
February 13 2024
Revision Received:
June 25 2024
Accepted:
August 07 2024
Citation
Yuanjiao Du, Xinyu Fan, Chunyu Song, Weiping Chang, Juan Xiong, Lin Deng, Wei-Ke Ji; Sec23IP recruits VPS13B/COH1 to ER exit site–Golgi interface for tubular ERGIC formation. J Cell Biol 2 December 2024; 223 (12): e202402083. doi: https://doi.org/10.1083/jcb.202402083
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