title: Proteomic Analysis of Loricrin Knockout Mouse Epidermis.
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.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rice
authors.forename: Blythe P
authors.initials: BP
authors.lastname: Durbin-Johnson
authors.affiliation: Department of Dermatology, Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ishitsuka
authors.forename: Michelle
authors.initials: M
authors.lastname: Salemi
authors.forename: Brett S
authors.initials: BS
authors.lastname: Phinney
authors.forename: David M
authors.initials: DM
authors.lastname: Rocke
authors.affiliation: Department of Dermatology, Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Roop
mesh_terms: D000818:Animals; D004817:Epidermis / Q000737:chemistry*; D000091344:Filaggrin Proteins; D007057:Ichthyosis; D053556:Keratin-1; D053550:Keratin-10; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D053556:Keratin-1; C507491:Krt10 protein, mouse; D008565:Membrane Proteins; D011506:Proteins; C064554:loricrin; D053550:Keratin-10
keywords: corneocyte; crosslinked envelopes; filaggrin; ichthyosis; isopeptide bonding; keratin; keratinocyte; label-free estimation; protein−protein interactions; transglutaminase