Title |
Abundance, complexation, and trafficking of Wnt/β-catenin signaling elements in response to Wnt3a
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Published in |
Journal of Molecular Signaling, October 2007
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DOI | 10.1186/1750-2187-2-11 |
Pubmed ID | |
Authors |
Noriko Yokoyama, Dezhong Yin, Craig C Malbon |
Abstract |
Wnt3a regulates a canonical signaling pathway in early development that controls the nuclear accumulation of beta-catenin and its activation of Lef/Tcf-sensitive transcription of developmentally important genes. Using totipotent mouse F9 teratocarcinoma cells expressing Frizzled-1 and biochemical analyses, we detail the influence of Wnt3a stimulation on the expression, complexation, and subcellular trafficking of key signaling elements of the canonical pathway, i.e., Dishevelled-2, Axin, glycogen synthase kinase-3beta, and beta-catenin. Cellular content of beta-catenin and Axin, and phospho-glycogen synthase kinase-3beta, but not Dishevelled-2, increases in response to Wnt3a. Subcellular localization of Axin in the absence of Wnt3a is symmetric, found evenly distributed among plasma membrane-, cytosol-, and nuclear-enriched fractions. Dishevelled-2, in contrast, is found predominately in the cytosol, whereas beta-catenin is localized to the plasma membrane-enriched fraction. Wnt3a stimulates trafficking of Dishevelled-2, Axin, and glycogen synthase kinase-3beta initially to the plasma membrane, later to the nucleus. Bioluminescence resonance energy transfer measurements reveal that complexes of Axin with Dishevelled-2, with glycogen synthase kinase-3beta, and with beta-catenin are demonstrable and they remain relatively stable in response to Wnt3a stimulation, although trafficking has occurred. Mammalian Dishevelled-1 and Dishevelled-2 display similar patterns of trafficking in response to Wnt3a, whereas that of Dishevelled-3 differs from the other two. This study provides a detailed biochemical analysis of signaling elements key to Wnt3a regulation of the canonical pathway. We quantify, for the first time, the Wnt-dependent regulation of cellular abundance and intracellular trafficking of these signaling molecules. In contrast, we observe little effect of Wnt3a stimulation on the level of protein-protein interactions among these constituents of Axin-based complexes themselves. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 5% |
Germany | 2 | 5% |
Japan | 1 | 2% |
Unknown | 37 | 88% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 13 | 31% |
Researcher | 7 | 17% |
Student > Master | 5 | 12% |
Student > Doctoral Student | 3 | 7% |
Lecturer | 2 | 5% |
Other | 7 | 17% |
Unknown | 5 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 15 | 36% |
Biochemistry, Genetics and Molecular Biology | 9 | 21% |
Medicine and Dentistry | 5 | 12% |
Unspecified | 1 | 2% |
Computer Science | 1 | 2% |
Other | 3 | 7% |
Unknown | 8 | 19% |