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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
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.
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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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