Department of Neurobiology, Harvard Medical School, Boston, United States
Edith P Karuna
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Ryan C Kunz
Department of Cell Biology, Harvard Medical School, Boston, United States
Taranjit S Gujral
Department of Systems Biology, Harvard Medical School, Boston, United States; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, United States
Andrea V Cantú
Department 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 States
Shannon S Choi
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Brigette Y Jong
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Kyoko Okada
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Michael K Scales
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Jennie Hum
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Linda S Hu
Department of Neurobiology, Harvard Medical School, Boston, United States
Department of Systems Biology, Harvard Medical School, Boston, United States
Ryuichi Nishinakamura
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
Soichiro Yamada
Department of Biomedical Engineering, University of California, Davis, United States
Diana J Laird
Department 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 States
Li-En Jao
Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
Steven P Gygi
Department of Cell Biology, Harvard Medical School, Boston, United States
Michael E Greenberg
Department of Neurobiology, Harvard Medical School, Boston, United States
Department of Neurobiology, Harvard Medical School, Boston, United States; Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, United States
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.
