title: Nanoscale architecture of cadherin-based cell adhesions.
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.
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bertocchi
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ravasio
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Yusuke
authors.identifier: http://orcid.org/0000-0002-2005-7704
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.
authors.forename: Talgat
authors.initials: T
authors.lastname: Sailov
authors.affiliation: National High Magnetic Field Laboratory, The Florida State University, Tallahassee, Florida 32310, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: National High Magnetic Field Laboratory, The Florida State University, Tallahassee, Florida 32310, USA.|Department of Biological Science, The Florida State University, Tallahassee, Florida 32306, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.|Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Republic of Singapore.
authors.forename: Ronen
authors.initials: R
authors.lastname: Zaidel-Bar
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.|Department of Biological Sciences, National University of Singapore, Singapore 117543, Republic of Singapore.|Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Republic of Singapore.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.|Institut Jacques Monod, Université Paris Diderot, CNRS UMR 7592, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Institut Jacques Monod, Université Paris Diderot, CNRS UMR 7592, Paris, France.
authors.forename: Rene-Marc
authors.initials: RM
authors.lastname: Mege
authors.affiliation: Mechanobiology Institute, Singapore 117411, Republic of Singapore.|Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Republic of Singapore.
authors.forename: Pakorn
authors.identifier: http://orcid.org/0000-0001-8765-3861
authors.initials: P
authors.lastname: Kanchanawong
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004285:Dogs; D007365:Intercellular Junctions / Q000378:metabolism; D007368:Interferometry; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008853:Microscopy; D053758:Nanoparticles / Q000737:chemistry*; D010766:Phosphorylation; D015398:Signal Transduction; D016596:Vinculin / Q000737:chemistry; D051178:alpha Catenin / Q000737:chemistry
chemical_list: D000199:Actins; D015415:Biomarkers; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D016596:Vinculin