Villaseca Soraya, Leal Juan Ignacio, Tovar Lina Mariana, Ruiz María José, Guajardo Jossef, Morales-Navarrete Hernan, Mayor Roberto, Torrejón Marcela
Laboratory of Signaling and Development, Group for the Study of Developmental Processes, Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, Universidad de Concepción, Casilla 160-C, Concepción, Chile.
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
Development. 2025 Apr 15;152(8). doi: 10.1242/dev.204235. Epub 2025 Apr 22.
Cell migration is crucial in embryonic development, tissue repair and cancer metastasis, driven by the actin and tubulin cytoskeletons that control cell shape, polarity, adhesion and movement in response to various cues. Although heterotrimeric G proteins are known to be involved in cell migration, the specific mechanisms, especially during development, remain elusive. This study examines the role of Gαi2, a heterotrimeric G-protein subunit, in cranial neural crest (NC) cell migration during Xenopus embryonic development. Our research reveals that Gαi2 interacts directly with the microtubule-associated protein EB1, regulating microtubule dynamics. We show that Gαi2 knockdown stabilizes microtubules, disrupts cell polarity and morphology, increases Rac1-GTP at the leading edge and cell-cell contacts, and impairs actin localization and focal adhesion disassembly. Additionally, RhoA-GTP is reduced at cell-cell contacts and concentrated at the leading edge in Gαi2 knockdown cells, providing evidence of a role for Gαi2 in polarity. Treatment with nocodazole, a microtubule-depolymerizing agent, reduces Rac1 activity, restoring cranial NC cell morphology, actin distribution and overall migration. Our findings highlight a crucial role for Gαi2 in cranial NC cell migration by modulating microtubule dynamics through EB1 and Rac1 activity.
细胞迁移在胚胎发育、组织修复和癌症转移中至关重要，由肌动蛋白和微管蛋白细胞骨架驱动，这些细胞骨架响应各种信号控制细胞形状、极性、黏附和运动。尽管已知异源三聚体G蛋白参与细胞迁移，但其具体机制，尤其是在发育过程中的机制，仍不清楚。本研究探讨了异源三聚体G蛋白亚基Gαi2在非洲爪蟾胚胎发育过程中颅神经嵴（NC）细胞迁移中的作用。我们的研究表明，Gαi2直接与微管相关蛋白EB1相互作用，调节微管动力学。我们发现，敲低Gαi2会使微管稳定，破坏细胞极性和形态，增加前缘和细胞间接触处的Rac1-GTP水平，并损害肌动蛋白定位和粘着斑解体。此外，在敲低Gαi2的细胞中，RhoA-GTP在细胞间接触处减少，在前缘集中，这为Gαi2在极性中的作用提供了证据。用微管解聚剂诺考达唑处理可降低Rac1活性，恢复颅神经嵴细胞形态、肌动蛋白分布和整体迁移。我们的研究结果突出了Gαi2在颅神经嵴细胞迁移中的关键作用，即通过EB1调节微管动力学和Rac1活性。
