Universität zu Köln

Shafraz, Omer, Ruebsam, Matthias, Stahley, Sara N., Caldara, Amber L., Kowalczyk, Andrew P., Niessen, Carien M. and Sivasankar, Sanjeevi ORCID: 0000-0003-2593-0477 (2018). E-cadherin binds to desmoglein to facilitate desmosome assembly. eLife, 7. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Desmosomes are adhesive junctions composed of two desmosomal cadherins: desmocollin (Dsc) and desmoglein (Dsg). Previous studies demonstrate that E-cadherin (Ecad), an adhesive protein that interacts in both trans (between opposing cells) and cis (on the same cell surface) conformations, facilitates desmosome assembly via an unknown mechanism. Here we use structure-function analysis to resolve the mechanistic roles of Ecad in desmosome formation. Using AFM force measurements, we demonstrate that Ecad interacts with isoform 2 of Dsg via a conserved Leu-175 on the Ecad cis binding interface. Super-resolution imaging reveals that Ecad is enriched in nascent desmosomes, supporting a role for Ecad in early desmosome assembly. Finally, confocal imaging demonstrates that desmosome assembly is initiated at sites of Ecad mediated adhesion, and that Ecad-L175 is required for efficient Dsg2 and desmoplakin recruitment to intercellular contacts. We propose that Ecad trans interactions at nascent cell-cell contacts initiate the recruitment of Dsg through direct cis interactions with Ecad which facilitates desmosome assembly.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shafraz, Omer UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruebsam, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Stahley, Sara N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Caldara, Amber L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kowalczyk, Andrew P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sivasankar, Sanjeevi UNSPECIFIED orcid.org/0000-0003-2593-0477 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-179778
DOI:	10.7554/eLife.37629
Journal or Publication Title:	eLife
Volume:	7
Date:	2018
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RIGHT-VENTRICULAR DYSPLASIA/CARDIOMYOPATHY; CELL-ADHESION; CLASSICAL CADHERINS; ADHERENS JUNCTIONS; MOLECULE; FORCE; KERATINOCYTES; COOPERATIVITY; ORGANIZATION; MAINTENANCE Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17977