The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled
| Autor: | Anita Grund, Anne M. Merks, Annette Borchers, Jakub Harnoš, Sarah F. S. Becker, Vítězslav Bryja, Marie-Claire Kratzer, Jubin Kashef, Klaudia Giehl |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
rac1 GTP-Binding Protein
Dishevelled Proteins RAC1 Biology Protein Serine-Threonine Kinases Xenopus Proteins Transfection 03 medical and health sciences Xenopus laevis 0302 clinical medicine Cranial neural crest Protein Domains Cell Movement Animals Guanine Nucleotide Exchange Factors Humans Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Morphant Cell migration Cell biology Dishevelled HEK293 Cells Phenotype chemistry Neural Crest 030220 oncology & carcinogenesis DEP domain Guanine nucleotide exchange factor Neural crest cell migration rhoA GTP-Binding Protein Developmental Biology Plasmids Protein Binding Signal Transduction |
| Zdroj: | Development (Cambridge, England). 147(10) |
| ISSN: | 1477-9129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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