A lecture taking place at the Crick.

: The Talin Code: Deciphering mechanotransduction using structural mechanobiology

Cell adhesion to the extracellular matrix (ECM), mediated by integrins, is exquisitely sensitive to biochemical, structural, and mechanical features of the ECM. Talin, the primary link between integrins and the actin cytoskeleton, coordinates the binding of a wide range of cytoskeletal and signaling adaptors in a force-dependent manner.

We envisage a talin molecule as a series of mechanochemical switches simultaneously decorated with numerous ligand proteins to form a signaling hub that we name the Mechanosensitive Signaling Hub (MSH). We propose that the talin MSH can integrate the magnitude and history of mechanical forces, the expression and activation state of ligand proteins, and its own post-translational modifications to determine adhesion structure and signaling outputs.

The ability of talin to parse diverse multiple inputs to determine robust, reproducible signaling responses leads us to view the role of talin as an MSH as a type of “code”; that is, a network of binding events organized in time and space that confers meaning in the form of signaling outputs. Such a “talin code” may explain how cells interpret complex chemical and physical information to coordinate their behaviors.

The ultimate goal of this project is to define in molecular and biophysical terms how physical forces transmitted via integrins regulate cell phenotype. By integrating biochemistry, structural biology and bioengineering, both in vitro and in vivo, we aim to decipher the talin mechanotransduction code at the atomic level.

References:

  • Goult BT, Yan J and Schwartz MA. (2018) Talin as a mechanical signaling hub. J. Cell Biol 217(11):3776-3784

Hosted by: Peter Cherepanov

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