The Ric-8a/G Alpha 13/Fak Signalling Cascade Controls Focal Adhesion Formation During Neural Crest Cell Migration In Xenopus

Ric-8A is a pleiotropic guanine nucleotide exchange factor involved in the activation of various heterotrimeric G-protein pathways during adulthood and early development. Here, we sought to determine the downstream effectors of Ric-8A during the migration of the vertebrate cranial neural crest (NC) cells. We show that the G alpha 13 knockdown phenocopies the Ric-8A morphant condition, causing actin cytoskeleton alteration, protrusion instability, and a strong reduction in the number and dynamics of focal adhesions. In addition, the overexpression of G alpha 13 is sufficient to rescue Ric-8A-depleted cells. Ric-8A and G alpha 13 physically interact and colocalize in protrusions of the cells leading edge. The focal adhesion kinase FAK colocalizes and interacts with the endogenous G alpha 13, and a constitutively active form of Src efficiently rescues the G alpha 13 morphant phenotype in NC cells. We propose that Ric-8A-mediated G alpha 13 signalling is required for proper cranial NC cell migration by regulating focal adhesion dynamics and protrusion formation.