Seminar: Dr. Johan de Rooij

Mechanotransduction at the Cadherin actomyosin interface

Date:
26 August 2014 00:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Mechanotransduction at the Cadherin actomyosin interface
Speaker(s):

Dr. Johan de Rooij, University Medical Center Utrecht, Dept. of Molecular Cancer Research

Host(s):

Dr. Alessandra Cambi, Dept. of Tumor Immunology, RIMLS

26-08-2014 00:00:00Europe/AmsterdamMechanotransduction at the Cadherin actomyosin interface Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Johan _de _RooijCells integrate chemical and mechanical information to orchestrate vital processes during tissue morphogenesis and remodeling. The identity of mechanoreceptors and their mechanisms of intracellular signaling, however, have remained largely enigmatic. By combining live cell imaging and biophysical experiments, we have identified the classical cadherin complex as a mechanosensor and showed that a-catenin and vinculin form the central mechanotransduction module. We identified a specific type of cadherin contact, the Focal Adherens Junction (FAJ), in which this mechanotransduction module reinforces cell-cell adhesion during tissue remodeling. To elucidate further mechanosensitive events at the cadherin complex, we have isolated tensile cadherin junctions and analyzed their content by mass spectrometry. This identified a set of actin-regulating proteins, including the LIM-domain proteins Zyxin and TES and their interaction partner VASP. We show that these proteins are myosinII-dependent members of FAJs, but that their recruitment is independent of the a-catenin-vinculin module. Thus, we uncovered that multiple mechanosensitive systems exist at the cadherin-actomyosin interface and that the regulation of actin dynamics is a prominent downstream function. Our current challenge is to understand the significance of these mechanisms for the morphogenesis of complex tissues. To this end we have generated zebrafish mutants of a-catenin and vinculin and we use organoid culture of salivary glands as an accessible model for branching morphogenesis.

Key publications:

  • Cadherin mechanotransduction in tissue remodeling. Cell Mol Life Sci. 70:4101-16, 2013. 
  • Vinculin associates with endothelial VE-cadherin junctions to control force- dependent remodeling. J.J Cell Biol. 196:641-52, 2012.
  • Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol. 28;189:1107-15, 2010.





 



<< back to all events