Proteomic analysis of loricrin knockout mouse epidermis

Robert H. Rice, Blythe P. Durbin-Johnson, Yosuke Ishitsuka, Michelle Salemi, Brett S. Phinney, David M Rocke, Dennis R. Roop

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The crosslinked envelope of the mammalian epidermal corneocyte serves as a scaffold for assembly of the lipid barrier of the epidermis. Thus, deficient envelope crosslinking by keratinocyte transglutaminase (TGM1) is a major cause of the human autosomal recessive congenital ichthyoses characterized by barrier defects. Expectations that loss of some envelope protein components would also confer an ichthyosis phenotype have been difficult to demonstrate. To help rationalize this observation, the protein profile of epidermis from loricrin knockout mice has been compared to that of wild type. Despite the mild phenotype of the knockout, some 40 proteins were incorporated into envelope material to significantly different extents compared to those of wild type. Nearly half were also incorporated to similarly altered extents into the disulfide bonded keratin network of the corneocyte. The results suggest that loss of loricrin alters their incorporation into envelopes as a consequence of protein-protein interactions during cell maturation. Mass spectrometric protein profiling revealed that keratin 1, keratin 10, and loricrin are prominent envelope components and that dozens of other proteins are also components. This finding helps rationalize the potential formation of functional envelopes, despite loss of a single component, due to the availability of many alternative transglutaminase substrates.

Original languageEnglish (US)
Pages (from-to)2560-2566
Number of pages7
JournalJournal of Proteome Research
Volume15
Issue number8
DOIs
StatePublished - Aug 5 2016

Keywords

  • corneocyte
  • crosslinked envelopes
  • filaggrin
  • ichthyosis
  • isopeptide bonding
  • keratin
  • keratinocyte
  • label-free estimation
  • protein-protein interactions
  • transglutaminase

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry

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  • Cite this

    Rice, R. H., Durbin-Johnson, B. P., Ishitsuka, Y., Salemi, M., Phinney, B. S., Rocke, D. M., & Roop, D. R. (2016). Proteomic analysis of loricrin knockout mouse epidermis. Journal of Proteome Research, 15(8), 2560-2566. https://doi.org/10.1021/acs.jproteome.6b00108