Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1
Abstract Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with dev...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55397-2 |
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| author | Fan Zhang Shaobai Li Hao Wu Shanshuang Chen |
| author_facet | Fan Zhang Shaobai Li Hao Wu Shanshuang Chen |
| author_sort | Fan Zhang |
| collection | DOAJ |
| description | Abstract Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl. Here, we show biochemical and structural evidence that human Vangl1 oligomerizes as dimers of trimers, and that the dimerization of trimers promotes binding to the PCP effector Prickle1 (Pk1) in vitro. Mapping of human disease-associated point mutations suggests potential pathological mechanisms and paves the way for future studies on the importance of lipid binding, central vestibule and oligomerization of Vangl, thereby providing insights into the molecular mechanisms of the PCP signaling pathway. |
| format | Article |
| id | doaj-art-e42bfd4445844fab80b71f9010dd8a7d |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e42bfd4445844fab80b71f9010dd8a7d2025-08-20T01:48:02ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-024-55397-2Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1Fan Zhang0Shaobai Li1Hao Wu2Shanshuang Chen3Shanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s HospitalShanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl. Here, we show biochemical and structural evidence that human Vangl1 oligomerizes as dimers of trimers, and that the dimerization of trimers promotes binding to the PCP effector Prickle1 (Pk1) in vitro. Mapping of human disease-associated point mutations suggests potential pathological mechanisms and paves the way for future studies on the importance of lipid binding, central vestibule and oligomerization of Vangl, thereby providing insights into the molecular mechanisms of the PCP signaling pathway.https://doi.org/10.1038/s41467-024-55397-2 |
| spellingShingle | Fan Zhang Shaobai Li Hao Wu Shanshuang Chen Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 Nature Communications |
| title | Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 |
| title_full | Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 |
| title_fullStr | Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 |
| title_full_unstemmed | Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 |
| title_short | Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1 |
| title_sort | cryo em structure and oligomerization of the human planar cell polarity core protein vangl1 |
| url | https://doi.org/10.1038/s41467-024-55397-2 |
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