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- Title
Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates.
- Authors
Susman, Michael W.; Karuna, Edith P.; Kunz, Ryan C.; Gujral, Taranjit S.; Cantú, Andrea V.; Choi, Shannon S.; Jong, Brigette Y.; Kyoko Okada; Scales, Michael K.; Hum, Jennie; Hu, Linda S.; Kirschner, Marc W.; Ryuichi Nishinakamura; Soichiro Yamada; Laird, Diana J.; Li-En Jao; Gygi, Steven P.; Greenberg, Michael E.; Hsin-Yi Henry Ho
- 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.
- Subjects
KINESIN; VERTEBRATES; IN vivo studies; MORPHOGENESIS; WNT signal transduction
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.26509