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First published online 24 September 2003
doi: 10.1242/dev.00737
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1 Department of Biochemistry, University of Washington, Seattle, WA 98195,
USA
2 Molecular and Cellular Biology Program, University of Washington, Seattle, WA
98195, USA
3 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell
Biology, Shanghai Institute for Biological Sciences, Shanghai, China
4 Department of Anatomy, University of California, San Francisco, CA 94143 and
Lawrence Berkeley National Laboratory, University of California, Berkeley, CA
94720, USA
5 Department of Genetics and Developmental Biology, University of Connecticut,
Farmington, CN 06030, USA
Author for correspondence (e-mail:
kimelman{at}u.washington.edu)
Accepted 23 July 2003
In Xenopus, axis development is initiated by dorsally elevated levels of cytoplasmic ß-catenin, an intracellular factor regulated by GSK3 kinase activity. Upon fertilization, factors that increase ß-catenin stability are translocated to the prospective dorsal side of the embryo in a microtubule-dependent process. However, neither the identity of these factors nor the mechanism of their movement is understood. Here, we show that the GSK3 inhibitory protein GBP/Frat binds kinesin light chain (KLC), a component of the microtubule motor kinesin. Upon egg activation, GBP-GFP and KLC-GFP form particles and exhibit directed translocation. KLC, through a previously uncharacterized conserved domain, binds a region of GBP that is required for GBP translocation and for GSK3 binding, and competes with GSK3 for GBP. We propose a model in which conventional kinesin transports a GBP-containing complex to the future dorsal side, where GBP dissociates and contributes to the local stabilization of ß-catenin by binding and inhibiting GSK3.
Key words: Frat, Wnt pathway, Axis specification, Cortical rotation, Microtubules
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