Developmental Cell
Volume 30, Issue 5, 8 September 2014, Pages 569-584
Journal home page for Developmental Cell

Article
Ena/VASP Proteins Cooperate with the WAVE Complex to Regulate the Actin Cytoskeleton

https://doi.org/10.1016/j.devcel.2014.08.001Get rights and content
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Highlights

  • Ena/VASP EVH1 interacts with the Abi subunit of the WRC

  • VASP enhances the ability of WRC to promote Arp2/3 actin assembly in presence of Rac

  • Ena/VASP and WRC interactions enhance cell migration

  • Drosophila photoreceptor axon targeting and oogenesis depends on Ena binding Abi

Summary

Ena/VASP proteins and the WAVE regulatory complex (WRC) regulate cell motility by virtue of their ability to independently promote actin polymerization. We demonstrate that Ena/VASP and the WRC control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi. This interaction increases cell migration and enables VASP to cooperatively enhance WRC stimulation of Arp2/3 complex-mediated actin assembly in vitro in the presence of Rac. Loss of this interaction in Drosophila macrophages results in defects in lamellipodia formation, cell spreading, and redistribution of Ena to the tips of filopodia-like extensions. Rescue experiments of abi mutants also reveals a physiological requirement for the Abi:Ena interaction in photoreceptor axon targeting and oogenesis. Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

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Co-second author

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Present address: Randall Division of Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK

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Present address: Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland

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Present address: College of Life Science, University of Dundee, Dundee DD1 5EH, UK