Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion.

Autor:	Damiano-Guercio J; Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany., Kurzawa L; CytoMorphoLab, Laboratoire de Physiologie cellulaire et Végétale, Interdisciplinary ResearchInstitute of Grenoble, CEA, CNRS, INRA, Grenoble-Alpes University, Grenoble, France.; CytomorphoLab, Hôpital Saint-Louis, Institut Universitaire d'Hematologie, UMRS1160, INSERM/AP-HP/UniversitéParis Diderot, Paris, France., Mueller J; Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria., Dimchev G; Division of Molecular Cell Biology, Zoological Institute, Technical University Braunschweig, Braunschweig, Germany., Schaks M; Division of Molecular Cell Biology, Zoological Institute, Technical University Braunschweig, Braunschweig, Germany.; Molecular Cell Biology Group, Helmholtz Centre for Infection Research, Braunschweig, Germany., Nemethova M; Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria., Pokrant T; Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany., Brühmann S; Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany., Linkner J; Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany., Blanchoin L; CytoMorphoLab, Laboratoire de Physiologie cellulaire et Végétale, Interdisciplinary ResearchInstitute of Grenoble, CEA, CNRS, INRA, Grenoble-Alpes University, Grenoble, France.; CytomorphoLab, Hôpital Saint-Louis, Institut Universitaire d'Hematologie, UMRS1160, INSERM/AP-HP/UniversitéParis Diderot, Paris, France., Sixt M; Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria., Rottner K; Division of Molecular Cell Biology, Zoological Institute, Technical University Braunschweig, Braunschweig, Germany.; Molecular Cell Biology Group, Helmholtz Centre for Infection Research, Braunschweig, Germany., Faix J; Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 May 11; Vol. 9. Date of Electronic Publication: 2020 May 11.
DOI:	10.7554/eLife.55351
Abstrakt:	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. Competing Interests: JD, LK, JM, GD, MS, MN, TP, SB, JL, LB, MS, KR, JF No competing interests declared (© 2020, Damiano-Guercio et al.)
Databáze:	MEDLINE
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