Mugdha Sawant
Threonine 150 phosphorylation of keratin 5 is linked to EBS and regulates filament assembly, cell cycle and oxidative stress response
Sawant, Mugdha; Schwarz, Nicole; Windoffer, Reinhard; Magin, Thomas; Krieger, Jan; Mucke, Norbert; Obara, Boguslaw; Jankowski, Vera; Jankowski, Joachim; Wally, Verena; Lettner, Thomas; Reichelt, Julia; Leube, Rudolf E.
Authors
Nicole Schwarz
Reinhard Windoffer
Thomas Magin
Jan Krieger
Norbert Mucke
Boguslaw Obara
Vera Jankowski
Joachim Jankowski
Verena Wally
Thomas Lettner
Julia Reichelt
Rudolf E. Leube
Abstract
A characteristic feature of the skin blistering disease epidermolysis bullosa simplex is keratin filament (KF) network collapse caused by aggregation of the basal epidermal keratin type II (KtyII) K5 and its type I partner keratin 14 (K14). Here, we examine the role of keratin phosphorylation in KF network rearrangement and cellular functions. We detect phosphorylation of the K5 head domain residue T150 in cytoplasmic epidermolysis bullosa simplex granules containing R125C K14 mutants. Expression of phosphomimetic T150D K5 mutants results in impaired KF formation in keratinocytes. The phenotype is enhanced upon combination with other phosphomimetic K5 head domain mutations. Remarkably, introduction of T150D K5 mutants into KtyII-lacking (KtyII–/–) keratinocytes prevents keratin network formation altogether. In contrast, phosphorylation-deficient T150A K5 leads to KFs with reduced branching and turnover. Assembly of T150D K5 is arrested at the heterotetramer stage coinciding with increased heat shock protein association. Finally, reduced cell viability and elevated response to stressors is noted in T150 mutant cells. Taken together, our findings identify T150 K5 phosphorylation as an important determinant of KF network formation and function with a possible role in epidermolysis bullosa simplex pathogenesis.
Citation
Sawant, M., Schwarz, N., Windoffer, R., Magin, T., Krieger, J., Mucke, N., …Leube, R. E. (2018). Threonine 150 phosphorylation of keratin 5 is linked to EBS and regulates filament assembly, cell cycle and oxidative stress response. Journal of Investigative Dermatology, 138(3), 627-636. https://doi.org/10.1016/j.jid.2017.10.011
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 8, 2017 |
Online Publication Date | Dec 6, 2017 |
Publication Date | Mar 1, 2018 |
Deposit Date | Sep 28, 2017 |
Publicly Available Date | Dec 6, 2019 |
Journal | Journal of Investigative Dermatology |
Print ISSN | 0022-202X |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 138 |
Issue | 3 |
Pages | 627-636 |
DOI | https://doi.org/10.1016/j.jid.2017.10.011 |
Files
Accepted Journal Article
(2.9 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by-nc-nd/4.0/
Copyright Statement
© 2018 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
You might also like
Segmentation of macular edema datasets with small residual 3D U-Net architectures
(2020)
Conference Proceeding
The relationship between curvilinear structure enhancement and ridge detection approaches
(2020)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search