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Cadherin flexibility provides a key difference between desmosomes and adherens junctions

DOI: 10.1073/pnas.1420508112 DOI Help

Authors: Humera Tariq (University of Manchester) , Jordi Bella (University of Manchester) , Thomas A. Jowitt (University of Manchester) , David F. Holmes (University of Manchester) , Mansour Rouhi (University of Manchester) , Zhuxiang Nie (University of Manchester) , Clair Baldock (University of Manchester) , David Garrod (University of Manchester) , Lydia Tabernero (University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 112 (17) , PAGES 5395 - 5400

State: Published (Approved)
Published: April 2015
Diamond Proposal Number(s): 4612

Abstract: Desmosomes and adherens junctions are intercellular adhesive structures essential for the development and integrity of vertebrate tissue, including the epidermis and heart. Their cell adhesion molecules are cadherins: type 1 cadherins in adherens junctions and desmosomal cadherins in desmosomes. A fundamental difference is that desmosomes have a highly ordered structure in their extracellular region and exhibit calcium-independent hyperadhesion, whereas adherens junctions appear to lack such ordered arrays, and their adhesion is always calcium-dependent. We present here the structure of the entire ectodomain of desmosomal cadherin desmoglein 2 (Dsg2), using a combination of small-angle X-ray scattering, electron microscopy, and solution-based biophysical techniques. This structure reveals that the ectodomain of Dsg2 is flexible even in the calcium-bound state and, on average, is shorter than the type 1 cadherin crystal structures. The Dsg2 structure has an excellent fit with the electron tomography reconstructions of human desmosomes. This fit suggests an arrangement in which desmosomal cadherins form trans interactions but are too far apart to interact in cis, in agreement with previously reported observations. Cadherin flexibility may be key to explaining the plasticity of desmosomes that maintain tissue integrity in their hyperadhesive form, but can adopt a weaker, calcium-dependent adhesion during wound healing and early development

Journal Keywords: Cadherins Desmosomes Adhesion Small-Angle X-Ray Scattering Structure

Subject Areas: Biology and Bio-materials


Instruments: I22-Small angle scattering & Diffraction

Added On: 10/07/2015 18:10

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