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

Toro-Tapia, G; Villaseca, S; Beyer, A; Roycroft, A; Marcellini, S; Mayor, R; Torrejón, M; (2018) The Ric-8A/Gα13/FAK signaling cascade controls focal adhesion formation during neural crest cell migration. Development , 145 (22) , Article dev164269. 10.1242/dev.164269. Green open access

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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.

Type: Article
Title: The Ric-8A/Gα13/FAK signaling cascade controls focal adhesion formation during neural crest cell migration
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.164269
Publisher version: https://doi.org/10.1242/dev.164269
Language: English
Additional information: This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cell migration, Focal adhesion, GEF, Heterotrimeric G-Protein, Neural crest, Protrusion formation, Ric-8A
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10058754
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