Cadherin mechanotransduction in tissue remodeling
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Cellular and Molecular Life Sciences
Review
Cadherin mechanotransduction in tissue remodeling Floor Twiss · Johan de Rooij
Received: 3 January 2013 / Revised: 19 March 2013 / Accepted: 19 March 2013 © Springer Basel 2013
Abstract Mechanical forces are increasingly recognized as central factors in the regulation of tissue morphogenesis and homeostasis. Central to the transduction of mechanical information into biochemical signaling is the contractile actomyosin cytoskeleton. Fluctuations in actomyosin contraction are sensed by tension sensitive systems at the interface between actomyosin and cell adhesion complexes. We review the current knowledge about the mechanical coupling of cell–cell junctions to the cytoskeleton and highlight the central role of α-catenin in this linkage. We assemble current knowledge about α-catenin’s regulation by tension and about its interactions with a diversity of proteins. We present a model in which α-catenin is a force-regulated platform for a machinery of proteins that orchestrates local cortical remodeling in response to force. Finally, we highlight recently described fundamental processes in tissue morphogenesis and argue where and how this α-catenin-dependent cadherin mechanotransduction may be involved. Keywords Cadherin · Mechanotransduction · α-catenin · Actomyosin · Morphogenesis · Development · Vinculin Abbreviations ΔVBS Delta vinculin binding site AJ Adherens junction ARP2/3 Actin-regulated protein CAM Cell adhesion molecule
F. Twiss · J. de Rooij (*) Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8, 3884 CT Utrecht, The Netherlands e-mail: [email protected] F. Twiss e-mail: [email protected]
Dsc Desmocollin Dsg Desmoglein EC Extracellular cadherin ECM Extracellular matrix EMT Epithelial to mesenchymal transition EPLIN Epithelial protein lost in neoplasia F-actin Filamentous actin FAJ Focal adherens junction FAK Focal adhesion kinase FH Formin homology HGF Hepatocyte growth factor JAM Junctional adhesion molecule LAJ Linear adherens junction MTC Magnetic twisting cytometry N-WASP Wiscott–Aldrich syndrome protein TJ Tight junction VASP Vasodilator-stimulated protein YAP Yes-associated protein ZA Zonula adherens ZAJ Zonula adherens junction ZO Zonula occludens
Introduction The ultimate goal of biological research is to understand the fundamental principles that govern the development and homeostasis of a multicellular organism. Developmental defects give rise to malformation disorders, and failure to maintain homeostasis leads to failure of organ systems and development of cancer. Knowing the underlying principles may lead to corrective treatments for disease prevention or cure. Moreover, with the current rapid advances in stem cell isolation, regenerative therapies to replace damaged organs have come within reach. In order to achieve organ
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F. Twiss, J. Rooij
regeneration, it will be important to understand the fundamental principles of organ development a
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