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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590807/ https://www.ncbi.nlm.nih.gov/pubmed/28885975 http://dx.doi.org/10.7554/eLife.26509 |
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author | Susman, Michael W Karuna, Edith P Kunz, Ryan C Gujral, Taranjit S Cantú, Andrea V Choi, Shannon S Jong, Brigette Y Okada, Kyoko Scales, Michael K Hum, Jennie Hu, Linda S Kirschner, Marc W Nishinakamura, Ryuichi Yamada, Soichiro Laird, Diana J Jao, Li-En Gygi, Steven P Greenberg, Michael E Ho, Hsin-Yi Henry |
author_facet | Susman, Michael W Karuna, Edith P Kunz, Ryan C Gujral, Taranjit S Cantú, Andrea V Choi, Shannon S Jong, Brigette Y Okada, Kyoko Scales, Michael K Hum, Jennie Hu, Linda S Kirschner, Marc W Nishinakamura, Ryuichi Yamada, Soichiro Laird, Diana J Jao, Li-En Gygi, Steven P Greenberg, Michael E Ho, Hsin-Yi Henry |
author_sort | Susman, Michael W |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-5590807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55908072017-09-11 Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates Susman, Michael W Karuna, Edith P Kunz, Ryan C Gujral, Taranjit S Cantú, Andrea V Choi, Shannon S Jong, Brigette Y Okada, Kyoko Scales, Michael K Hum, Jennie Hu, Linda S Kirschner, Marc W Nishinakamura, Ryuichi Yamada, Soichiro Laird, Diana J Jao, Li-En Gygi, Steven P Greenberg, Michael E Ho, Hsin-Yi Henry eLife Developmental Biology and Stem Cells 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. eLife Sciences Publications, Ltd 2017-09-08 /pmc/articles/PMC5590807/ /pubmed/28885975 http://dx.doi.org/10.7554/eLife.26509 Text en © 2017, Susman et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology and Stem Cells Susman, Michael W Karuna, Edith P Kunz, Ryan C Gujral, Taranjit S Cantú, Andrea V Choi, Shannon S Jong, Brigette Y Okada, Kyoko Scales, Michael K Hum, Jennie Hu, Linda S Kirschner, Marc W Nishinakamura, Ryuichi Yamada, Soichiro Laird, Diana J Jao, Li-En Gygi, Steven P Greenberg, Michael E Ho, Hsin-Yi Henry Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates |
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 | Developmental Biology and Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590807/ https://www.ncbi.nlm.nih.gov/pubmed/28885975 http://dx.doi.org/10.7554/eLife.26509 |
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