Skip Navigation

Publication Detail

Title: A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Authors: Kumar, Vinod; Bouameur, Jamal-Eddine; Bär, Janina; Rice, Robert H; Hornig-Do, Hue-Tran; Roop, Dennis R; Schwarz, Nicole; Brodesser, Susanne; Thiering, Sören; Leube, Rudolf E; Wiesner, Rudolf J; Vijayaraj, Preethi; Brazel, Christina B; Heller, Sandra; Binder, Hans; Löffler-Wirth, Henry; Seibel, Peter; Magin, Thomas M

Published In J Cell Biol, (2015 Dec 07)

Abstract: Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation.

PubMed ID: 26644517 Exiting the NIEHS site

MeSH Terms: Animals; Cell Adhesion; Cell Membrane/metabolism; Cornified Envelope Proline-Rich Proteins/metabolism; DNA-Binding Proteins/metabolism; Epidermis/metabolism*; Female; Gene Expression Regulation, Developmental; Genotype; Intermediate Filaments/metabolism; Keratinocytes/metabolism; Keratins/metabolism*; Lipids/chemistry*; Male; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria/metabolism*; Proteome/metabolism; Transcription Factors/metabolism

Back
to Top