Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility.
Cell motility requires lamellipodial protrusion, a process driven by actin polymerization. Ena/VASP proteins accumulate in protruding lamellipodia and promote the rapid actin-driven motility of the pathogen Listeria. In contrast, Ena/VASP negatively regulate cell translocation. To resolve this paradox, we analyzed the function of Ena/VASP during lamellipodial protrusion. Ena/VASP-deficient lamellipodia protruded slower but more persistently, consistent with their increased cell translocation rates. Actin networks in Ena/VASP-deficient lamellipodia contained shorter, more highly branched filaments compared to controls. Lamellipodia with excess Ena/VASP contained longer, less branched filaments. In vitro, Ena/VASP promoted actin filament elongation by interacting with barbed ends, shielding them from capping protein. We conclude that Ena/VASP regulates cell motility by controlling the geometry of actin filament networks within lamellipodia.
Bear
James E
JE
Massachusetts Institute of Technology, Department of Biology, Cambridge 02139, USA.
Svitkina
Tatyana M
TM
Krause
Matthias
M
Schafer
Dorothy A
DA
Loureiro
Joseph J
JJ
Strasser
Geraldine A
GA
Maly
Ivan V
IV
Chaga
Oleg Y
OY
Cooper
John A
JA
Borisy
Gary G
GG
Gertler
Frank B
FB
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051345:Destrin; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008863:Microspheres; D010750:Phosphoproteins / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D000098662:Vasodilator-Stimulated Phosphoprotein
D051339:Actin Depolymerizing Factors; D000199:Actins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D051345:Destrin; C092744:ENA-VASP proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011108:Polymers; D000098662:Vasodilator-Stimulated Phosphoprotein