Nanoscale architecture of cadherin-based cell adhesions. Nature Cell Biology, December 2016

By Cristina Bertocchi1, Yilin Wang1, Andrea Ravasio1, Yusuke Hara1, Yao Wu1, Talgat Sailov1, Michelle A. Baird2, Michael W. Davidson2,3, Ronen Zaidel-Bar1,4, Yusuke Toyama1,5,6, Benoit Ladoux1,7, Rene-Marc Mege7 & Pakorn Kanchanawong1,4

Nature Cell Biology. December 2016. 19(1). 28-37. doi: 10.1038/ncb3456.

Abstract

Multicellularity in animals requires dynamic maintenance of cell-cell contacts. Intercellularly ligated cadherins recruit numerous proteins to form supramolecular complexes that connect with the actin cytoskeleton and support force transmission. However, the molecular organization within such structures remains unknown. Here we mapped protein organization in cadherin-based adhesions by super-resolution microscopy, revealing a multi-compartment nanoscale architecture, with the plasma-membrane-proximal cadherin-catenin compartment segregated from the actin cytoskeletal compartment, bridged by an interface zone containing vinculin. Vinculin position is determined by α-catenin, and following activation, vinculin can extend ∼30 nm to bridge the cadherin-catenin and actin compartments, while modulating the nanoscale positions of the actin regulators zyxin and VASP. Vinculin conformational activation requires tension and tyrosine phosphorylation, regulated by Abl kinase and PTP1B phosphatase. Such modular architecture provides a structural framework for mechanical and biochemical signal integration by vinculin, which may differentially engage cadherin-catenin complexes with the actomyosin machinery to regulate cell adhesions.

 

1Mechanobiology Institute, Singapore.
2National High Magnetic Field Laboratory, The Florida State University, USA.
3Department of Biological Science, The Florida State University, USA.
4Department of Biomedical Engineering, National University of Singapore, Singapore.
5Department of Biological Sciences, National University of Singapore, Singapore.
6Temasek Life Sciences Laboratory, National University of Singapore, Singapore.
7Institut Jacques Monod, Université Paris Diderot, France.