TY - JOUR
T1 - Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility
AU - Bear, James E.
AU - Svitkina, Tatyana M.
AU - Krause, Matthias
AU - Schafer, Dorothy A.
AU - Loureiro, Joseph J.
AU - Strasser, Geraldine A.
AU - Maly, Ivan V.
AU - Chaga, Oleg Y.
AU - Cooper, John A.
AU - Borisy, Gary G.
AU - Gertler, Frank B.
N1 - Funding Information:
We thank Gretchen Baltus, Amber Murray, and Christy Canida for excellent technical support and Douglas Rubinson for help with statistical analysis. We thank R. Rohatgi and M. Kirschner for the kind gift of the N-WASP antibody. We thank Sally Zigmond, Doug Lauffenburger, and Velia Fowler for helpful suggestions and comments. Work from D.A.S. and J.A.C. was supported by National Institutes of Health grant GM38542 to J.A.C. Work from T.M.S., I.V.M., O.Y.C., and G.G.B. was supported by NIH grant GM62431 to G.G.B. J.J.L. is supported by the Anna Fuller Molecular Oncology Fund. J.E.B. is supported by a Special Fellow award from the Leukemia and Lymphoma Society (3476-02). This work was supported by NIH Glue Grant on Cell Migration IU54 GM63126 (G.G.B. and F.B.G.), by NIH grant GM58801, by funds from Merck & Co., and by the WM Keck Distinguished Young Scholar Award to F.B.G.
PY - 2002/5/17
Y1 - 2002/5/17
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/18444389953
U2 - 10.1016/S0092-8674(02)00731-6
DO - 10.1016/S0092-8674(02)00731-6
M3 - Article
C2 - 12086607
AN - SCOPUS:18444389953
SN - 0092-8674
VL - 109
SP - 509
EP - 521
JO - Cell
JF - Cell
IS - 4
ER -