Kinesin-2 and IFT-A act as a complex promoting nuclear localization of β-catenin during Wnt signalling
| العنوان: | Kinesin-2 and IFT-A act as a complex promoting nuclear localization of β-catenin during Wnt signalling |
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| المؤلفون: | Sophie Balmer, Marek Mlodzik, Davide Esposito, Carlo Iomini, Stuart A. Aaronson, Linh T. Vuong |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Science, Mutant, Active Transport, Cell Nucleus, Kinesins, General Physics and Astronomy, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Mediator, Microtubule, Animals, Drosophila Proteins, Wings, Animal, RNA, Small Interfering, lcsh:Science, Wnt Signaling Pathway, beta Catenin, Armadillo Domain Proteins, Cell Nucleus, Multidisciplinary, Chemistry, Wnt signaling pathway, General Chemistry, Cell biology, Wnt Proteins, Protein Transport, 030104 developmental biology, Cytoplasm, Catenin, Kinesin, Drosophila, RNA Interference, lcsh:Q, sense organs, Carrier Proteins, 030217 neurology & neurosurgery, Nuclear localization sequence, Signal Transduction |
| الوصف: | Wnt/Wg-signalling is critical signalling in all metazoans. Recent studies suggest that IFT-A proteins and Kinesin-2 modulate canonical Wnt/Wg-signalling independently of their ciliary role. Whether they function together in Wnt-signalling and their mechanistic role in the pathway remained unresolved. Here we demonstrate that Kinesin-2 and IFT-A proteins act as a complex during Drosophila Wg-signalling, affecting pathway activity in the same manner, interacting genetically and physically, and co-localizing with β-catenin, the mediator of Wnt/Wg-signalling on microtubules. Following pathway activation, Kinesin-2/IFT-A mutant cells exhibit high cytoplasmic β-catenin levels, yet fail to activate Wg-targets. In mutant tissues in both, Drosophila and mouse/MEFs, nuclear localization of β-catenin is markedly reduced. We demonstrate a conserved, motor-domain dependent function of the Kinesin-2/IFT-A complex in promoting nuclear translocation of β-catenin. We show that this is mediated by protecting β-catenin from a conserved cytoplasmic retention process, thus identifying a mechanism for Kinesin-2/IFT-A in Wnt-signalling that is independent of their ciliary role. IFT-A proteins and Kinesin-2 modulate canonical Wnt/Wg-signalling independent of their ciliary role, but how is unclear. Here, the authors show that Kinesin-2 and IFT-A act as a complex to promote nuclear translocation of β-catenin in Drosophila and mouse MEF Wnt signalling independent of its ciliary role. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96a77d88fd8afdbd292a669b9771f29d http://link.springer.com/article/10.1038/s41467-018-07605-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....96a77d88fd8afdbd292a669b9771f29d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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