Physics-Biology interface seminar: Christophe Le Clainche

Regulation of actin assembly and mechanotransduction in cell-matrix adhesion complexes: a biochemical study of the talin-vinculin complex

Christophe Le Clainche (I2BC, Gif-sur-Yvette)

Cell migration is involved in many physiological and pathological processes. Force is produced by the growth and the contraction of the actin cytoskeleton (1). To produce force in adherent cells, these actin networks must be anchored to the extracellular matrix (ECM) by adhesion complexes (1,2). These structures contain transmembrane integrins that mechanically couple the ECM to the intracellular actin cytoskeleton via actin binding proteins (ABPs) (2). This system acts as a molecular clutch that controls force transmission across adhesion complexes. This molecular clutch is a complex interface made of multiple layers of regulated protein-protein interactions (2). The multiple activities of the ABPs present in these structures play a critical role in the dynamics of this interface. In addition to the control of actin filament binding and polymerization (1-3), these proteins sense and respond to the force applied by the actomyosin cytoskeleton to adjust the anchoring strength (4,5). Our goal is to determine the molecular mechanisms by which these ABPs cooperate to control the mechanical coupling between the actin cytoskeleton and cell-matrix adhesion complexes.

To study these ABPs, our laboratory combines the measurement of actin polymerisation kinetics in fluorescence spectroscopy, single actin filament observations in TIRF microscopy and the reconstitution of actin-based mechanosensitive processes on micropatterned surfaces. Our model system is the mechanosensitive complex made of the two ABPs talin and vinculin.
Our results showed that vinculin controls actin filament elongation (3). More recent results revealed that talin also regulates actin polymerisation in response to integrin binding (unpublished data). In addition, we have developed a microscopy assay with pure proteins in which the self-assembly of actomyosin cables controls the association of vinculin to a talin-micropatterned surface in a reversible manner (4, 5). This in vitro reconstitution revealed the mechanism by which a key mechanosensitive molecular switch senses and controls the connection between adhesion complexes and the actomyosin cytoskeleton.

References

  • (1) Christophe Le Clainche and Marie-France Carlier.
    Regulation of actin assembly associated with protrusion and adhesion in cell migration.
    Physiological Reviews (2008) Apr;88(2):489-513.
  • (2) Corina Ciobanasu, Bruno Faivre, Christophe Le Clainche.
    Integrating actin dynamics, mechanotransduction and integrin activation: The multiple functions of actin binding proteins in focal adhesions.
    European Journal of Cell Biology (2013) (92) 339-348.
  • (3) Christophe Le Clainche, Satya P Dwivedi, Dominique Didry, Marie-France Carlier.
    Vinculin is a dually regulated actin filament barbed-end capping and side-binding protein.
    Journal of Biological Chemistry (2010) Jul 23;285(30):23420-32.
  • (4) Corina Ciobanasu, Bruno Faivre, Christophe Le Clainche.
    Actomyosin dependent formation of the mechanosensitive talin-vinculin complex reinforces actin anchoring.
    Nature Communications (2014) 5:3095
  • (5) Corina Ciobanasu, Bruno Faivre, Christophe Le Clainche.
    Reconstituting actomyosin-dependent mechanosensitive protein complexes in vitro.
    Nature Protocols (2015) Jan ;10(1):75-89

Date/Time : 05/10/2015 - 11:00 - 12:00

Location : Moyen Amphi, Building 510, Université Paris-Sud Orsay

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