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Author Notes:

Correspondence to: Shuyi Nie, E-mail: shuyi.nie@biology.gatech.edu

We would like to thank Dr Marianne Bronner (California Institute of Technology, Pasadena, USA) for her comments and discussion.

We would also like to acknowledge the support from the National Institutes of Health, National Science Foundation, and Georgia Institute of Technology.

Conflict of interest: none declared.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • actin cytoskeleton
  • neural crest
  • Rho GTPases
  • Cdc42 effector protein 1
  • cell migration
  • MYOSIN-II
  • DIRECTIONAL MIGRATION
  • EFFECTOR PROTEINS
  • FIBROBLAST
  • FAMILY
  • LAMELLIPODIA
  • BLEBS
  • BORG5
  • RAC

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

Tools:

Journal Title:

Journal of Molecular Cell Biology

Volume:

Volume 10, Number 5

Publisher:

, Pages 376-387

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017 The Author.

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