Cdc42 regulates the cellular localization of Cdc42ep1 in controlling neural crest cell migration

• Type of Material: Article
• Authors: Shlomi Cohen, Georgia Institute of Technology; Daniel T. Kovari, Emory University; Wenbin Wei, Georgia Institute of Technology; Rebecca Keate, Georgia Institute of Technology; Jennifer Curtis, Emory University; Shuyi Nie, Georgia Institute of Technology
• Language: English
• Date: 2018-10-01
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author.
• Final Published Version (URL): http://dx.doi.org/10.1093/jmcb/mjx044
• Title of Journal or Parent Work: Journal of Molecular Cell Biology
• ISSN: 1674-2788
• Volume: 10
• Issue: 5
• Start Page: 376
• End Page: 387
• Grant/Funding Information: This work is supported by the National Institutes of Health (R00DE022796 to S.N.) and National Science Foundation (DMR-0955811 to J.E.C. and PHY-0848797 to J.E.C. and D.T.K.).
• Keywords: actin cytoskeleton; DIRECTIONAL MIGRATION; cell migration; Science & Technology; MYOSIN-II; BORG5; Cdc42 effector protein 1; FIBROBLAST; Rho GTPases; BLEBS; neural crest; Cell Biology; FAMILY; LAMELLIPODIA; Life Sciences & Biomedicine; RAC; EFFECTOR PROTEINS
• Research Categories: Biology, Cell; Engineering, Biomedical; Chemistry, Physical

Abstract

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.