TY - JOUR
T1 - Vinculin-actin interaction couples actin retrograde flow to focal adhesions, but is dispensable for focal adhesion growth
AU - Thievessen, Ingo
AU - Thompson, Peter M.
AU - Berlemont, Sylvain
AU - Plevock, Karen M.
AU - Plotnikov, Sergey V.
AU - Zemljic-Harpf, Alice
AU - Ross, Robert S.
AU - Davidson, Michael W.
AU - Danuser, Gaudenz
AU - Campbell, Sharon L.
AU - Waterman, Clare M.
PY - 2013
Y1 - 2013
N2 - In migrating cells, integrin-based focal adhesions (FAs) assemble in protruding lamellipodia in association with rapid filamentous actin (F-actin) assembly and retrograde flow. How dynamic F-actin is coupled to FA is not known. We analyzed the role of vinculin in integrating Factin and FA dynamics by vinculin gene disruption in primary fibroblasts. Vinculin slowed F-actin flow in maturing FA to establish a lamellipodium-lamellum border and generate high extracellular matrix (ECM) traction forces. In addition, vinculin promoted nascent FA formation and turnover in lamellipodia and inhibited the frequency and rate of FA maturation. Characterization of a vinculin point mutant that specifically disrupts Factin binding showed that vinculin-F-actin interaction is critical for these functions. However, FA growth rate correlated with F-actin flow speed independently of vinculin. Thus, vinculin functions as a molecular clutch, organizing leading edge F-actin, generating ECM traction, and promoting FA formation and turnover, but vinculin is dispensible for FA growth.
AB - In migrating cells, integrin-based focal adhesions (FAs) assemble in protruding lamellipodia in association with rapid filamentous actin (F-actin) assembly and retrograde flow. How dynamic F-actin is coupled to FA is not known. We analyzed the role of vinculin in integrating Factin and FA dynamics by vinculin gene disruption in primary fibroblasts. Vinculin slowed F-actin flow in maturing FA to establish a lamellipodium-lamellum border and generate high extracellular matrix (ECM) traction forces. In addition, vinculin promoted nascent FA formation and turnover in lamellipodia and inhibited the frequency and rate of FA maturation. Characterization of a vinculin point mutant that specifically disrupts Factin binding showed that vinculin-F-actin interaction is critical for these functions. However, FA growth rate correlated with F-actin flow speed independently of vinculin. Thus, vinculin functions as a molecular clutch, organizing leading edge F-actin, generating ECM traction, and promoting FA formation and turnover, but vinculin is dispensible for FA growth.
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U2 - 10.1083/jcb.201303129
DO - 10.1083/jcb.201303129
M3 - Article
C2 - 23836933
AN - SCOPUS:84880642716
SN - 0021-9525
VL - 202
SP - 163
EP - 177
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -