The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32366678
DOI
10.1242/dev.186338
PII: dev.186338
Knihovny.cz E-resources
- Keywords
- Cadherin-11, Dishevelled, GEF Trio, Neural crest cell migration, Rho GTPases, Xenopus,
- MeSH
- Neural Crest cytology embryology MeSH
- Phenotype MeSH
- HEK293 Cells MeSH
- Humans MeSH
- Plasmids genetics MeSH
- Cell Movement genetics MeSH
- Dishevelled Proteins genetics metabolism MeSH
- Protein Serine-Threonine Kinases genetics metabolism MeSH
- Protein Domains MeSH
- Xenopus Proteins genetics metabolism MeSH
- rac1 GTP-Binding Protein metabolism MeSH
- rhoA GTP-Binding Protein metabolism MeSH
- Signal Transduction genetics MeSH
- Transfection MeSH
- Protein Binding genetics MeSH
- Guanine Nucleotide Exchange Factors genetics metabolism MeSH
- Xenopus laevis embryology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DVL1 protein, Xenopus MeSH Browser
- DVL2 protein, human MeSH Browser
- Dvl2 protein, Xenopus MeSH Browser
- Dishevelled Proteins MeSH
- Protein Serine-Threonine Kinases MeSH
- Xenopus Proteins MeSH
- rac1 GTP-Binding Protein MeSH
- rhoA GTP-Binding Protein MeSH
- TRIO protein, human MeSH Browser
- Guanine Nucleotide Exchange Factors MeSH
Directional migration during embryogenesis and tumor progression faces the challenge that numerous external signals need to converge to precisely control cell movement. The Rho guanine exchange factor (GEF) Trio is especially well suited to relay signals, as it features distinct catalytic domains to activate Rho GTPases. Here, we show that Trio is required for Xenopus cranial neural crest (NC) cell migration and cartilage formation. Trio cell-autonomously controls protrusion formation of NC cells and Trio morphant NC cells show a blebbing phenotype. Interestingly, the Trio GEF2 domain is sufficient to rescue protrusion formation and migration of Trio morphant NC cells. We show that this domain interacts with the DEP/C-terminus of Dishevelled (DVL). DVL - but not a deletion construct lacking the DEP domain - is able to rescue protrusion formation and migration of Trio morphant NC cells. This is likely mediated by activation of Rac1, as we find that DVL rescues Rac1 activity in Trio morphant embryos. Thus, our data provide evidence for a novel signaling pathway, whereby Trio controls protrusion formation of cranial NC cells by interacting with DVL to activate Rac1.
Department of Experimental Biology Faculty of Science Masaryk University Brno 62500 Czech Republic
Max Delbrück Center for Molecular Medicine in the Helmholtz Association 13125 Berlin Germany
Philipps Universität Marburg Faculty of Biology Molecular Embryology 35043 Marburg Germany
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