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J Mol Cell Biol January 1, 2018; 10 (5): 376-387.
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Cdc42 regulates the cellular localization of Cdc42ep1 in controlling neural crest cell migration.

Cohen S , Kovari DT , Wei W , Keate R , Curtis JE , Nie S .

The member of Rho family of small GTPases Cdc42 plays important and conserved roles in cell polarity and motility. The Cdc42ep family proteins have been identified to bind to Cdc42, yet how they interact with Cdc42 to regulate cell migration remains to be elucidated. In this study, we focus on Cdc42ep1, which is expressed predominantly in the highly migratory neural crest cells in frog embryos. Through morpholino-mediated knockdown, we show that Cdc42ep1 is required for the migration of cranial neural crest cells. Loss of Cdc42ep1 leads to rounder cell shapes and the formation of membrane blebs, consistent with the observed disruption in actin organization and focal adhesion alignment. As a result, Cdc42ep1 is critical for neural crest cells to apply traction forces at the correct place to migrate efficiently. We further show that Cdc42ep1 is localized to two areas in neural crest cells: in membrane protrusions together with Cdc42 and in perinuclear patches where Cdc42 is absent. Cdc42 directly interacts with Cdc42ep1 (through the CRIB domain) and changes in Cdc42 level shift the distribution of Cdc42ep1 between these two subcellular locations, controlling the formation of membrane protrusions and directionality of migration as a consequence. These results suggest that Cdc42ep1 elaborates Cdc42 activity in neural crest cells to promote their efficient migration.

PubMed ID: 29040749
PMC ID: PMC6692865
Article link: J Mol Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdc42 dnai1 rho utrn
GO keywords: neural crest cell migration [+]

Article Images: [+] show captions
References [+] :
Alfandari, Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin. 2003, Pubmed, Xenbase