Gαi2 Interaction with EB1 controls microtubule dynamics and Rac1 activity in Xenopus neural crest cell migration.

Abstract

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 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 Gαi2 role in polarity. Nocodazole treatment, a microtubule-depolymerizing agent, reduces Rac1 activity, restoring cranial NC cell morphology, actin distribution, and overall migration. Our findings highlight Gαi2 crucial role in cranial NC cell migration by modulating microtubule dynamics through EB1 and Rac1 activity.