Détails de la réservation
- Le : 10 April 2017
- De : 14 h 00
- à : 16 h 00
- Salle : Salle de conférence
Détails de l'évènement
Ben GOULT
(School of Biosciences, University of Kent, United Kingdom.
- https://www.kent.ac.uk/bio/profiles/staff/goult.html)
"Emerging role FOR talin as a mechanosensitive signalling platform"
Résumé
Adhesions between cells and the surrounding extracellular matrix (ECM) are fundamental to the development of multicellular life and is mediated by the integrin family of cell surface receptors.
The central role of talin as a cytoplasmic adapter protein in these cell-matrix adhesions is well established; activating integrins enabling cell-ECM attachment and coupling integrins to the actin cytoskeleton. In this scenario talin is perfectly positioned to act as a mechanosensor sensing external mechanical stimuli and converting them into intracellular biological signals.
Our recent work on the mechanical properties of talin shows that it acts as a mechanosensitive signalling platform (MSP). The mechanosensing functions of talin rely on conformational changes in the multiple talin rod domains in response to force, that regulate interactions between talin and other cellular factors. By stretching single talin molecules using magnetic tweezers we have characterised the mechanical response of talin and identified two stages of talin mechanosensing. An initial unfolding event in domain R3 is a key regulatory checkpoint involved in adhesion assembly. Here, force dependent conformational changes in R3 result in the recruitment of vinculin, which triggers adhesion maturation. This initial unfolding event happens at a force of just 5 pN.
However, once the adhesion has formed our data reveal the emerging role of talin as an MSP. The other 12 talin rod domains unfold at forces between 7-20 pN and we have identified that each one of these domains binds different signalling molecules in their folded and unfolded states. These discrete conformational changes enable talin to serve as a platform able to recruit numerous signalling molecules in a context dependent fashion. This enables many differential signalling complexes to form under different scenarios (different integrins, cell types, matrix stiffness etc.).
This talk will outline the emerging concept of talin as a mechanosensitive signalling platform and suggest that signalling through talin might be one of the key signalling mechanisms in integrin-mediated adhesion.
Invited by Olivier Rossier and Greg Giannone
Responsable
- Nom : Rossier olivier