The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled

0540503 - BFÚ 2021 RIV GB eng J - Článek v odborném periodiku
Kratzer, M.-C. - Becker, S. F. S. - Grund, A. - Merks, A. - Harnoš, J. - Bryja, Vítězslav - Giehl, K. - Kashef, J. - Borchers, A.
The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled.
Development. Roč. 147, č. 10 (2020), č. článku dev186338. ISSN 0950-1991. E-ISSN 1477-9129
Institucionální podpora: RVO:68081707
Klíčová slova: intellectual disability * signaling pathways * beta-catenin * gef domain * xenopus * rac
Obor OECD: Developmental biology
Impakt faktor: 6.868, rok: 2020
Způsob publikování: Open access
https://dev.biologists.org/content/147/10/dev186338

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 Reel, 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.
Trvalý link: http://hdl.handle.net/11104/0318124