Orchestrated control of filaggrin-actin scaffolds underpins cornification

Danuta Gutowska-Owsiak , Jorge Bernardino de La Serna , Marco Fritzsche , Aishath Naeem , Ewa I. Podobas , Michael Leeming , Huw Colin-York , Ryan O’Shaughnessy , Christian Eggeling , Graham S. Ogg


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.
Author Danuta Gutowska-Owsiak (IFB / M020 / DMCB)
Danuta Gutowska-Owsiak,,
- Department of Molecular and Cellular Biology
, Jorge Bernardino de La Serna
Jorge Bernardino de La Serna,,
, Marco Fritzsche
Marco Fritzsche,,
, Aishath Naeem
Aishath Naeem,,
, Ewa I. Podobas
Ewa I. Podobas,,
, Michael Leeming
Michael Leeming,,
, Huw Colin-York
Huw Colin-York,,
, Ryan O’Shaughnessy
Ryan O’Shaughnessy,,
, Christian Eggeling
Christian Eggeling,,
, Graham S. Ogg
Graham S. Ogg,,
Journal seriesCell Death & Disease, ISSN 2041-4889, (A 35 pkt)
Issue year2018
Publication size in sheets0.85
Article number412
ASJC Classification1306 Cancer Research; 1307 Cell Biology; 2403 Immunology; 2804 Cellular and Molecular Neuroscience
URL https://www.nature.com/articles/s41419-018-0407-2.pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)35
Score sourcejournalList
ScoreMinisterial score = 35.0, 13-02-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.407; WoS Impact Factor: 2018 = 5.959 (2) - 2018=6.211 (5)
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