Universität zu Köln

Kumar, Vinod ORCID: 0000-0002-7167-0402, Bouameur, Jamal-Eddine, Baer, Janina, Rice, Robert H., Hornig-Do, Hue-Tran, Roop, Dennis R., Schwarz, Nicole ORCID: 0000-0001-7888-6970, Brodesser, Susanne, Thiering, Soeren, Leube, Rudolf E., Wiesner, Rudolf J., Brazel, Christina B., Heller, Sandra, Binder, Hans, Loeffler-Wirth, Henry, Seibel, Peter and Magin, Thomas M. (2015). A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. J. Cell Biol., 211 (5). S. 1057 - 1076. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kumar, Vinod UNSPECIFIED orcid.org/0000-0002-7167-0402 UNSPECIFIED Bouameur, Jamal-Eddine UNSPECIFIED UNSPECIFIED UNSPECIFIED Baer, Janina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rice, Robert H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hornig-Do, Hue-Tran UNSPECIFIED UNSPECIFIED UNSPECIFIED Roop, Dennis R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Nicole UNSPECIFIED orcid.org/0000-0001-7888-6970 UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiering, Soeren UNSPECIFIED UNSPECIFIED UNSPECIFIED Leube, Rudolf E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brazel, Christina B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heller, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Binder, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeffler-Wirth, Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED Seibel, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Magin, Thomas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383879
DOI:	10.1083/jcb.201404147
Journal or Publication Title:	J. Cell Biol.
Volume:	211
Number:	5
Page Range:	S. 1057 - 1076
Date:	2015
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPIDERMOLYSIS-BULLOSA SIMPLEX; ELECTRON-TRANSPORT CHAIN; MICE LACKING; STRATUM-CORNEUM; CORNIFIED ENVELOPE; ATOPIC-DERMATITIS; TERMINAL DIFFERENTIATION; INTERMEDIATE-FILAMENTS; GENETIC ARCHITECTURE; MULTIPLE ALLERGIES Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38387