Regulation of actin assembly and mechanotransduction in cell-matrix adhesion complexes: a biochemical study of the talin-vinculin complex
| Dates: | 25 November 2014 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Christophe Le Clainche |
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This seminar is part of the Tissue Systems seminar series. Cell migration is involved in many physiological and pathological processes. Cells use the force produced by actin polymerization and actomyosin contraction for movement. To produce force, the actin cytoskeleton is mechanically coupled to the extracellular matrix (ECM). Actin binding proteins (ABPs), frequently clustered in adhesion complexes, play a critical role in ECM-actin coupling. Among the few ABPs that have been characterised in adhesion complexes, some proteins regulate actin nucleation, association and elongation. Others proteins modulate actin binding and dynamics in a mechanosensitive manner. Our goal is to determine the molecular mechanisms by which these ABPs cooperate to control actin anchoring in adhesion complexes, and consequently migration speed.
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 results showed that vinculin controls actin filament elongation. More recent results revealed that talin also regulates actin polymerisation. 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. This in vitro reconstitution revealed the mechanism by which a key molecular switch senses and controls the connection between adhesion complexes and the actomyosin cytoskeleton.
Speaker
Christophe Le Clainche
Organisation: Laboratoire d'Enzymologie et Biochimie Structurales
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Lecture Theatre
Michael Smith Building
Manchester
