Gαi2-Mediated Regulation of Microtubules Dynamics and Rac1 Activity Orchestrates Cranial Neural Crest Cell Migration in Xenopus

During cell migration, a complex process intricately influenced by chemical and mechanical cues, the actin and tubulin cytoskeletons serve as central players, dictating cell morphology, polarity, focal adhesion dynamics, and overall motility. Despite the well-established involvement of heterotrimeric G proteins in cell migration, the precise underlying mechanism remains elusive. This study delves into the intricacies of Gαi2 role in cranial neural crest cell migration, revealing its interaction with tubulin and microtubule-associated proteins like EB1 and EB3, suggesting a regulatory function in microtubule dynamics modulation. Gαi2 knockdown led to stabilized microtubules, altered cell morphology, disrupted polarity, increased Rac1-GTP concentration at the leading edge and cell-cell contacts, distorted Par3 and ζPKC localization and impaired cortical actin localization and focal adhesion disassembly. Significantly, treatment with nocodazole, a microtubule-depolymerizing agent, effectively decreased Rac1 activity and rescued cranial neural crest cell morphology, actin distribution, and overall cell migration. Our findings shed light on the intricate molecular mechanisms underlying cranial neural crest cell migration and highlight the pivotal role of Gαi2 in orchestrating microtubule dynamics through EB1 and EB3, modulating Rac1 activity during this crucial developmental process.

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