Kinesin superfamily protein kif26b links wnt5a-ror signaling to the control of cell and tissue behaviors in vertebrates

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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/b-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitinproteasome 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.

Original languageEnglish (US)
Article numbere26509
JournaleLife
Volume6
DOIs
StatePublished - Sep 8 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Kinesin superfamily protein kif26b links wnt5a-ror signaling to the control of cell and tissue behaviors in vertebrates'. Together they form a unique fingerprint.

  • Cite this

    Susman, M. W., Karuna, E. P., Kunz, R. C., Gujral, T. S., Cantú, A. V., Choi, S. S., Jong, B. Y., Okada, K., Scales, M. K., Hum, J., Hu, L. S., Kirschner, M. W., Nishinakamura, R., Yamada, S., Laird, D. J., Jao, L-E., Gygi, S. P., Greenberg, M. E., & Ho, H-Y. H. (2017). Kinesin superfamily protein kif26b links wnt5a-ror signaling to the control of cell and tissue behaviors in vertebrates. eLife, 6, [e26509]. https://doi.org/10.7554/eLife.26509