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Orchestrated control of filaggrin-actin scaffolds underpins cornification.

Gutowska-Owsiak, Danuta and Bernardino de la Serna, Jorge and Fritzsche, Marco and Podobas, Ewa Izabela and Naeem, Aishath and Leeming, Michael and Colin-York, Huw and O’Shaughnessy, Ryan and Eggeling, Christian and Ogg, Graham (2018) Orchestrated control of filaggrin-actin scaffolds underpins cornification. Cell Death and Disease, 9(4) (412). pp. 1-18.

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Official URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC58545...

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.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Biophysics
ID Code:1541
Deposited By: PhD EI Podobas
Deposited On:11 Jun 2018 07:34
Last Modified:11 Jun 2018 07:34

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