title: Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1.
abstract: Profilaggrin is a large epidermal polyprotein that is proteolytically processed during keratinocyte differentiation to release multiple filaggrin monomer units as well as a calcium-binding regulatory NH2-terminal filaggrin S-100 protein. We show that epidermal deficiency of the transmembrane serine protease Matriptase/MT-SP1 perturbs lipid matrix formation, cornified envelope morphogenesis, and stratum corneum desquamation. Surprisingly, proteomic analysis of Matriptase/MT-SP1-deficient epidermis revealed the selective loss of both proteolytically processed filaggrin monomer units and the NH2-terminal filaggrin S-100 regulatory protein. This was associated with a profound accumulation of profilaggrin and aberrant profilaggrin-processing products in the stratum corneum. The data identify keratinocyte Matriptase/MT-SP1 as an essential component of the profilaggrin-processing pathway and a key regulator of terminal epidermal differentiation.
authors.affiliation: Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: List
authors.forename: Roman
authors.initials: R
authors.lastname: Szabo
authors.forename: Philip W
authors.initials: PW
authors.lastname: Wertz
authors.forename: Julie
authors.initials: J
authors.lastname: Segre
authors.forename: Christian C
authors.initials: CC
authors.lastname: Haudenschild
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003681:Dehydration / Q000201:enzymology; D004817:Epidermis / Q000201:enzymology* / Q000254:growth & development* / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D007057:Ichthyosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D050356:Lipid Metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010447:Peptide Hydrolases / Q000172:deficiency / Q000235:genetics; D010539:Permeability; D011498:Protein Precursors / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics; D012868:Skin Abnormalities / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014357:Trypsin / Q000172:deficiency* / Q000235:genetics
chemical_list: D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D009418:S100 Proteins; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C485595:matriptase; C118992:St14 protein, mouse; D014357:Trypsin