期刊
DEVELOPMENT
卷 145, 期 22, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.164269
关键词
Ric-8A; Cell migration; Heterotrimeric G-Protein; Focal adhesion; GEF; Protrusion formation; Neural crest
资金
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1140394, 1180926]
- Medical Research Council [M010465, J000655]
- Biotechnology and Biological Sciences Research Council [M008517]
- Wellcome Trust
- BBSRC [BB/R00627X/1] Funding Source: UKRI
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.
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