Till Katharina, Borchers Annette
Department of Biology, Molecular Embryology, Philipps-University Marburg, Karl-von-Frisch-Straße 8, 35043 Marburg, Germany.
Development. 2025 May 1;152(9). doi: 10.1242/dev.204446. Epub 2025 May 6.
Neural crest (NC) cells are highly migratory cells that contribute to a wide range of vertebrate tissues and must respond to a variety of external signals to precisely control directed cell migration. The RhoGEF Trio is particularly well suited to relay signals to the cytoskeleton because it contains two GEF domains that activate Rac1 and RhoA, respectively. Previously, we have shown that Trio is dynamically localized in Xenopus NC cells and required for their migration. However, how its distinct enzymatic functions are spatially controlled remains unclear. Here, we show that Trio is required for contact inhibition of locomotion (CIL), a phenomenon whereby NC cells change their polarity and directionality upon cell-cell contact. At cell-cell contacts, Trio interacts with Ptk7, a regulator of planar cell polarity that we have recently shown to be required for CIL. Our data suggest that Ptk7 inhibits the Rac1 activity of Trio, thereby limiting Trio activity to the activation of RhoA and promoting CIL.
神经嵴（NC）细胞是高度迁移性的细胞，对多种脊椎动物组织有贡献，并且必须响应各种外部信号以精确控制定向细胞迁移。Rho鸟嘌呤核苷酸交换因子（RhoGEF）Trio特别适合将信号传递到细胞骨架，因为它包含两个分别激活Rac1和RhoA的鸟嘌呤核苷酸交换因子（GEF）结构域。此前，我们已经表明Trio在非洲爪蟾神经嵴细胞中动态定位，并且是其迁移所必需的。然而，其独特的酶功能如何在空间上受到控制仍不清楚。在这里，我们表明Trio是运动接触抑制（CIL）所必需的，CIL是一种现象，即神经嵴细胞在细胞间接触时改变其极性和方向性。在细胞间接触时，Trio与Ptk7相互作用，Ptk7是平面细胞极性的调节剂，我们最近表明它是CIL所必需的。我们的数据表明，Ptk7抑制Trio的Rac1活性，从而将Trio的活性限制在RhoA的激活，并促进CIL。
