TY - JOUR
T1 - Talin and vinculin combine their activities to trigger actin assembly
AU - Wang, Hong
AU - Said, Rayan
AU - Nguyen-Vigouroux, Clémence
AU - Henriot, Véronique
AU - Gebhardt, Peter
AU - Pernier, Julien
AU - Grosse, Robert
AU - Le Clainche, Christophe
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Focal adhesions (FAs) strengthen their link with the actin cytoskeleton to resist force. Talin-vinculin association could reinforce actin anchoring to FAs by controlling actin polymerization. However, the actin polymerization activity of the talin-vinculin complex is not known because it requires the reconstitution of the mechanical and biochemical activation steps that control the association of talin and vinculin. By combining kinetic and binding assays with single actin filament observations in TIRF microscopy, we show that the association of talin and vinculin mutants, mimicking mechanically stretched talin and activated vinculin, triggers a sequential mechanism in which filaments are nucleated, capped and released to elongate. In agreement with these observations, FRAP experiments in cells co-expressing the same constitutive mutants of talin and vinculin revealed accelerated growth of stress fibers. Our findings suggest a versatile mechanism for the regulation of actin assembly in FAs subjected to various combinations of biochemical and mechanical cues.
AB - Focal adhesions (FAs) strengthen their link with the actin cytoskeleton to resist force. Talin-vinculin association could reinforce actin anchoring to FAs by controlling actin polymerization. However, the actin polymerization activity of the talin-vinculin complex is not known because it requires the reconstitution of the mechanical and biochemical activation steps that control the association of talin and vinculin. By combining kinetic and binding assays with single actin filament observations in TIRF microscopy, we show that the association of talin and vinculin mutants, mimicking mechanically stretched talin and activated vinculin, triggers a sequential mechanism in which filaments are nucleated, capped and released to elongate. In agreement with these observations, FRAP experiments in cells co-expressing the same constitutive mutants of talin and vinculin revealed accelerated growth of stress fibers. Our findings suggest a versatile mechanism for the regulation of actin assembly in FAs subjected to various combinations of biochemical and mechanical cues.
U2 - 10.1038/s41467-024-53859-1
DO - 10.1038/s41467-024-53859-1
M3 - Article
C2 - 39489770
AN - SCOPUS:85208498875
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 9497
ER -