Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion.
Actin Capping Proteins
/ metabolism
Actin Cytoskeleton
/ metabolism
Actin-Related Protein 2-3 Complex
/ metabolism
Actins
/ metabolism
Animals
CRISPR-Cas Systems
Cell Adhesion
Cell Line, Tumor
Cell Movement
DNA-Binding Proteins
/ genetics
Fibroblasts
Focal Adhesions
Gene Knockout Techniques
Integrins
/ metabolism
Melanoma, Experimental
Mice
NIH 3T3 Cells
Polymerization
Pseudopodia
/ physiology
Recombinant Proteins
/ genetics
Ena/VASP proteins
cell adhesion
cell biology
cell migration
filopodia
lamellipodia
microspikes
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
11 05 2020
11 05 2020
Historique:
received:
21
01
2020
accepted:
08
05
2020
pubmed:
12
5
2020
medline:
17
3
2021
entrez:
12
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32391788
doi: 10.7554/eLife.55351
pii: 55351
pmc: PMC7239657
doi:
pii:
Substances chimiques
Actin Capping Proteins
0
Actin-Related Protein 2-3 Complex
0
Actins
0
DNA-Binding Proteins
0
ENA-VASP proteins
0
Integrins
0
Recombinant Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : FA 330/11-1
Pays : International
Organisme : H2020 European Research Council
ID : AAA 741773
Pays : International
Organisme : H2020 European Research Council
ID : CoG 724373
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : RO2414/5-1
Pays : International
Organisme : Technische Universität Braunschweig
ID : GRK2223/1
Pays : International
Informations de copyright
© 2020, Damiano-Guercio et al.
Déclaration de conflit d'intérêts
JD, LK, JM, GD, MS, MN, TP, SB, JL, LB, MS, KR, JF No competing interests declared
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