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Article Dans Une Revue Journal of Biological Chemistry Année : 2018

Integrin-bound talin head inhibits actin filament barbed end elongation

Résumé

Focal adhesions (FAs) mechanically couple the extracellular matrix (ECM) to the dynamic actin cytoskeleton, via transmembrane integrins and actin-binding proteins. The molecular mechanisms by which protein machineries control force transmission along this molecular axis, i.e. modulating integrin activation and controlling actin polymerization, remain largely unknown. Talin is a major actin-binding protein that controls both the inside-out activation of integrins and actin-filament anchoring and thus plays a major role in the establishment of the actin-ECM mechanical coupling. Talin contains three actin-binding domains (ABDs). The N-terminal head domain contains both the F3 integrin-activating domain and ABD1, while the C-terminal rod contains the actin-anchoring ABD2 and ABD3. Integrin binding is regulated by an intramolecular interaction between the N-terminal head and a C-terminal five-helix-bundle (R9). Whether talin ABDs regulate actin polymerization in a constitutive or regulated manner has not been fully explored. Here, we combine kinetics assays using fluorescence spectroscopy and single actin filament observation in TIRF microscopy, to examine relevant functions of the three ABDs of talin. We find that the N-terminal ABD1 blocks actin filament barbed end elongation while ABD2 and ABD3 do not show any activity. By mutating residues in ABD1, we find that this activity is mediated by a positively charged surface that is partially masked by its intramolecular interaction with R9. Our results also demonstrate that, once this intramolecular interaction is released, integrin-bound talin head retains the ability to inhibit actin assembly.

Dates et versions

hal-02176994 , version 1 (08-07-2019)

Identifiants

Citer

Corina Ciobanasu, Hong Wang, Véronique Henriot, Cécile Mathieu, Annabelle Fente, et al.. Integrin-bound talin head inhibits actin filament barbed end elongation. Journal of Biological Chemistry, 2018, 293 (7), pp.2586--2596. ⟨10.1074/jbc.M117.808204⟩. ⟨hal-02176994⟩
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