A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity
© 2015 Kumar et al..
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.
| Errataetall: |
ErratumIn: J Cell Biol. 2016 Mar 28;212(7):877. - PMID 27002167 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:211 |
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| Enthalten in: |
The Journal of cell biology - 211(2015), 5 vom: 07. Dez., Seite 1057-75 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kumar, Vinod [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.04.2016 Date Revised 13.11.2018 published: Print ErratumIn: J Cell Biol. 2016 Mar 28;212(7):877. - PMID 27002167 Citation Status MEDLINE |
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| doi: |
10.1083/jcb.201404147 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM255352573 |
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| 100 | 1 | |a Kumar, Vinod |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a ErratumIn: J Cell Biol. 2016 Mar 28;212(7):877. - PMID 27002167 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 Kumar et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Cornified Envelope Proline-Rich Proteins |2 NLM | |
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| 700 | 1 | |a Bouameur, Jamal-Eddine |e verfasserin |4 aut | |
| 700 | 1 | |a Bär, Janina |e verfasserin |4 aut | |
| 700 | 1 | |a Rice, Robert H |e verfasserin |4 aut | |
| 700 | 1 | |a Hornig-Do, Hue-Tran |e verfasserin |4 aut | |
| 700 | 1 | |a Roop, Dennis R |e verfasserin |4 aut | |
| 700 | 1 | |a Schwarz, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Brodesser, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Thiering, Sören |e verfasserin |4 aut | |
| 700 | 1 | |a Leube, Rudolf E |e verfasserin |4 aut | |
| 700 | 1 | |a Wiesner, Rudolf J |e verfasserin |4 aut | |
| 700 | 1 | |a Vijayaraj, Preethi |e verfasserin |4 aut | |
| 700 | 1 | |a Brazel, Christina B |e verfasserin |4 aut | |
| 700 | 1 | |a Heller, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Binder, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Löffler-Wirth, Henry |e verfasserin |4 aut | |
| 700 | 1 | |a Seibel, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Magin, Thomas M |e verfasserin |4 aut | |
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