The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled
The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled
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DOI：
10.1242/dev.186338
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发表时间：
2020-05-01
期刊：
影响因子：
4.6
通讯作者：
Borchers, Annette
中科院分区：
文献类型：
--
作者：
Kratzer, Marie-Claire;Becker, Sarah F. S.;Borchers, Annette
胚胎发生和肿瘤进展过程中的定向迁移面临着许多外部信号需要收敛以精确控制细胞运动的挑战。Rho鸟嘌呤交换因子（GEF）Trio特别适合于传递信号，因为它具有不同的催化结构域来激活Rho GTP酶。在这里，我们表明，三是所需的爪蟾颅神经嵴（NC）细胞迁移和软骨形成。Trio细胞自主控制NC细胞的突起形成，Trio morphant NC细胞显示出起泡表型。有趣的是，Trio GEF 2结构域足以挽救Trio morphant NC细胞的突起形成和迁移。我们发现，这个域与DEP/C-末端Dishevelled（DVL）相互作用。DVL -但不是缺乏DEP结构域的缺失构建体-能够拯救三态吗啡样NC细胞的突起形成和迁移。这可能是通过激活Reel介导的，因为我们发现DVL挽救了Trio morphant胚胎中的Rac 1活性。因此，我们的数据提供了一种新的信号通路的证据，即Trio通过与DVL相互作用来激活Rac 1，从而控制颅NC细胞的突起形成。
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.