The Ric-8A/Gα13/FAK signaling cascade controls focal adhesion formation during neural crest cell migration

Abstract

Ric-8A is a pleiotropic guanine nucleotide exchange factor involved 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 Gα13 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 Gα13 is sufficient to rescue Ric-8A depleted cells. Ric-8A and Gα13 physically interact and co-localize in protrusions of the cells leading edge. The focal adhesion kinase FAK co-localizes and interacts with the endogenous Gα13, and a constitutively active form of Src efficiently rescues the Gα13 morphant phenotype in NC cells. We propose that Ric-8A-mediated Gα13 signaling is required for proper cranial NC cell migration by regulating focal adhesion dynamics and protrusion formation.