Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates
Wnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/26509 |
| _version_ | 1811180660700741632 |
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| author | Michael W Susman Edith P Karuna Ryan C Kunz Taranjit S Gujral Andrea V Cantú Shannon S Choi Brigette Y Jong Kyoko Okada Michael K Scales Jennie Hum Linda S Hu Marc W Kirschner Ryuichi Nishinakamura Soichiro Yamada Diana J Laird Li-En Jao Steven P Gygi Michael E Greenberg Hsin-Yi Henry Ho |
| author_facet | Michael W Susman Edith P Karuna Ryan C Kunz Taranjit S Gujral Andrea V Cantú Shannon S Choi Brigette Y Jong Kyoko Okada Michael K Scales Jennie Hum Linda S Hu Marc W Kirschner Ryuichi Nishinakamura Soichiro Yamada Diana J Laird Li-En Jao Steven P Gygi Michael E Greenberg Hsin-Yi Henry Ho |
| author_sort | Michael W Susman |
| collection | DOAJ |
| description | Wnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin superfamily protein Kif26b as a downstream target of the Wnt5a-Ror pathway. Wnt5a-Ror, through a process independent of the canonical Wnt/β-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitin-proteasome system. Through this mechanism, Kif26b modulates the migratory behavior of cultured mesenchymal cells in a Wnt5a-dependent manner. Genetic perturbation of Kif26b function in vivo caused embryonic axis malformations and depletion of primordial germ cells in the developing gonad, two phenotypes characteristic of disrupted Wnt5a-Ror signaling. These findings indicate that Kif26b links Wnt5a-Ror signaling to the control of morphogenetic cell and tissue behaviors in vertebrates and reveal a new role for regulated proteolysis in noncanonical Wnt5a-Ror signal transduction. |
| first_indexed | 2024-04-11T09:06:51Z |
| format | Article |
| id | doaj.art-275601caa693448db8ac74e33e0585f8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:51Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-275601caa693448db8ac74e33e0585f82022-12-22T04:32:36ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.26509Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebratesMichael W Susman0https://orcid.org/0000-0001-8635-283XEdith P Karuna1Ryan C Kunz2Taranjit S Gujral3Andrea V Cantú4Shannon S Choi5Brigette Y Jong6Kyoko Okada7Michael K Scales8Jennie Hum9Linda S Hu10Marc W Kirschner11https://orcid.org/0000-0001-6540-6130Ryuichi Nishinakamura12Soichiro Yamada13Diana J Laird14Li-En Jao15Steven P Gygi16Michael E Greenberg17Hsin-Yi Henry Ho18https://orcid.org/0000-0002-8780-7864Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United States; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United StatesDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, JapanDepartment of Biomedical Engineering, University of California, Davis, United StatesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, United StatesDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesDepartment of Cell Biology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United States; Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United StatesWnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin superfamily protein Kif26b as a downstream target of the Wnt5a-Ror pathway. Wnt5a-Ror, through a process independent of the canonical Wnt/β-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitin-proteasome system. Through this mechanism, Kif26b modulates the migratory behavior of cultured mesenchymal cells in a Wnt5a-dependent manner. Genetic perturbation of Kif26b function in vivo caused embryonic axis malformations and depletion of primordial germ cells in the developing gonad, two phenotypes characteristic of disrupted Wnt5a-Ror signaling. These findings indicate that Kif26b links Wnt5a-Ror signaling to the control of morphogenetic cell and tissue behaviors in vertebrates and reveal a new role for regulated proteolysis in noncanonical Wnt5a-Ror signal transduction.https://elifesciences.org/articles/26509noncanonical Wnt signalingRorsignal transductiontissue morphogenesisregulated proteolysisKif26b |
| spellingShingle | Michael W Susman Edith P Karuna Ryan C Kunz Taranjit S Gujral Andrea V Cantú Shannon S Choi Brigette Y Jong Kyoko Okada Michael K Scales Jennie Hum Linda S Hu Marc W Kirschner Ryuichi Nishinakamura Soichiro Yamada Diana J Laird Li-En Jao Steven P Gygi Michael E Greenberg Hsin-Yi Henry Ho Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates eLife noncanonical Wnt signaling Ror signal transduction tissue morphogenesis regulated proteolysis Kif26b |
| title | Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
| title_full | Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
| title_fullStr | Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
| title_full_unstemmed | Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
| title_short | Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
| title_sort | kinesin superfamily protein kif26b links wnt5a ror signaling to the control of cell and tissue behaviors in vertebrates |
| topic | noncanonical Wnt signaling Ror signal transduction tissue morphogenesis regulated proteolysis Kif26b |
| url | https://elifesciences.org/articles/26509 |
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