Proteomic analysis of desmosomes reveals novel components required for epidermal integrity.

Published

Journal Article

Desmosomes are cell-cell adhesions necessary for the maintenance of tissue integrity in the skin and heart. While the core components of desmosomes have been identified, peripheral components that modulate canonical or noncanonical desmosome functions still remain largely unexplored. Here we used targeted proximity labeling approaches to further elaborate the desmosome proteome in epidermal keratinocytes. Quantitative mass spectrometry analysis identified all core desmosomal proteins while uncovering a diverse array of new constituents with broad molecular functions. By individually targeting the inner and outer dense plaques, we defined proteins enriched within these subcompartments. We validated a number of these novel desmosome-associated proteins and find that many are membrane proximal proteins that show a dependence on functional desmosomes for their cortical localization. We further explored the mechanism of localization and function of two novel desmosome-associated adaptor proteins enriched in the desmosome proteome, Crk and Crk-like (CrkL). These proteins interacted with Dsg1 and rely on Dsg1 and desmoplakin for robust cortical localization. Epidermal deletion of both Crk and CrkL resulted in perinatal lethality with defects in desmosome morphology and keratin organization, thus demonstrating the utility of this dataset in identifying novel proteins required for desmosome-dependent epidermal integrity.

Full Text

Duke Authors

Cited Authors

  • Badu-Nkansah, KA; Lechler, T

Published Date

  • May 15, 2020

Published In

Volume / Issue

  • 31 / 11

Start / End Page

  • 1140 - 1153

PubMed ID

  • 32238101

Pubmed Central ID

  • 32238101

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

Digital Object Identifier (DOI)

  • 10.1091/mbc.E19-09-0542

Language

  • eng

Conference Location

  • United States