Journal article
Orchestrated control of filaggrin–actin scaffolds underpins cornification
- Abstract:
- Epidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate. We employed advanced (super-resolution) microscopy to examine filaggrin organization and dynamics in skin and human keratinocytes during differentiation. We found that filaggrin organization depends on the cytoplasmic actin cytoskeleton, including the role for α- and β-actin scaffolds. Filaggrin-containing KHGs displayed high mobility and migrated toward the nucleus during differentiation. Pharmacological disruption targeting actin networks resulted in granule disintegration and accelerated cornification. We identified the role of AKT serine/threonine kinase 1 (AKT1), which controls binding preference and function of heat shock protein B1 (HspB1), facilitating the switch from actin stabilization to filaggrin processing. Our results suggest an extended model of cornification in which filaggrin utilizes actins to effectively control keratinocyte differentiation and death, promoting epidermal stratification and formation of a fully functional skin barrier.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 5.0MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41419-018-0407-2
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Cell Death and Disease More from this journal
- Volume:
- 9
- Issue:
- 2018
- Pages:
- 412
- Publication date:
- 2018-03-15
- Acceptance date:
- 2018-02-08
- DOI:
- EISSN:
-
2041-4889
- ISSN:
-
2041-4889
- Pubs id:
-
pubs:829789
- UUID:
-
uuid:31b9c8b3-d0e2-4630-82f6-2262d19814cd
- Local pid:
-
pubs:829789
- Source identifiers:
-
829789
- Deposit date:
-
2018-03-15
Terms of use
- Copyright holder:
- © Gutowska-Owsiak, et al
- Copyright date:
- 2018
- Notes:
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record