Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates

Autor: Hsin-Yi Henry Ho, Ryan C. Kunz, Michael K Scales, Ryuichi Nishinakamura, Shannon S. Choi, Taranjit S. Gujral, Li-En Jao, Jennie Hum, Soichiro Yamada, Kyoko Okada, Andrea V. Cantú, Steven P. Gygi, Diana J. Laird, Edith P. Karuna, Brigette Y Jong, Michael E. Greenberg, Linda Hu, Michael W. Susman, Marc W. Kirschner
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Proteomics
Mouse
regulated proteolysis
Kinesins
Inbred C57BL
Regenerative Medicine
Mice
Morphogenesis
Developmental
Biology (General)
Wnt Signaling Pathway
beta Catenin
General Neuroscience
Wnt signaling pathway
Ror
Gene Expression Regulation
Developmental
Kinesin
General Medicine
Embryonic Tissue
Cell biology
embryonic structures
Medicine
Stem cell
Signal transduction
signal transduction
tissue morphogenesis
Research Article
QH301-705.5
Science
1.1 Normal biological development and functioning
Embryonic Development
Biology
Receptor Tyrosine Kinase-like Orphan Receptors
General Biochemistry
Genetics and Molecular Biology
Wnt-5a Protein
Cell Line
03 medical and health sciences
developmental biology
stem cells
Underpinning research
noncanonical Wnt signaling
Animals
Humans
mouse
General Immunology and Microbiology
Stem Cell Research
Embryonic stem cell
body regions
Mice
Inbred C57BL
030104 developmental biology
Developmental Biology and Stem Cells
HEK293 Cells
Gene Expression Regulation
Kif26b
Biochemistry and Cell Biology
sense organs
Developmental biology
Zdroj: eLife
eLife, Vol 6 (2017)
ISSN: 2050-084X
Popis: 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.
Databáze: OpenAIRE
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