E-cadherin binds to desmoglein to facilitate desmosome assembly

ELife
Omer ShafrazSanjeevi Sivasankar

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.

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Citations

Jun 28, 2019·Cellular and Molecular Life Sciences : CMLS·Marcin MochRudolf E Leube
Aug 14, 2019·EMBO Reports·Keith T Woodley, Mark O Collins
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Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Omer ShafrazSanjeevi Sivasankar
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Mar 28, 2021·Cancer Letters·Hyeong-Jun HanYong-Nyun Kim
Dec 24, 2020·Acta Physiologica·Marie-Therès WanuskeVolker Spindler
May 26, 2021·Journal of Structural Biology·Fiyaz Mohammed, Martyn Chidgey
Jul 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ramesh KoiralaSanjeevi Sivasankar
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Methods Mentioned

BETA
force
fluorescence microscopy
AFM
force measurements
FRET
confocal microscopy
transfection
co-immunoprecipitation
FCS
PCR

Software Mentioned

Fiji
ImageJ
Elements
NIS

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