Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion
Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.
Article and author information
Deutsche Forschungsgemeinschaft (FA 330/11-1)
- Jan Faix
H2020 European Research Council (AAA 741773)
- Laurent Blanchoin
H2020 European Research Council (CoG 724373)
- Michael Sixt
Deutsche Forschungsgemeinschaft (RO2414/5-1)
- Klemens Rottner
Technische Universität Braunschweig (GRK2223/1)
- Klemens Rottner
Austrian Science Fund
- Michael Sixt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Pekka Lappalainen, University of Helsinki, Finland
- Received: January 21, 2020
- Accepted: May 8, 2020
- Accepted Manuscript published: May 11, 2020 (version 1)
- Version of Record published: May 20, 2020 (version 2)
© 2020, Damiano- Guercio et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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