Akinduro, O;
Sully, K;
Patel, A;
Robinson, DJ;
Chikh, A;
McPhail, G;
Braun, KM;
... Bergamaschi, D; + view all
(2016)
Constitutive autophagy and nucleophagy during epidermal differentiation.
Journal of Investigative Dermatology
, 136
(7)
pp. 1460-1470.
10.1016/j.jid.2016.03.016.
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Abstract
Epidermal keratinocytes migrate through the epidermis up to the granular layer where, upon terminal differentiation they progressively loose organelles and convert into anucleate cells or corneocytes. Our report explores the role of autophagy in ensuring epidermal function providing the first comprehensive profile of autophagy marker expression in developing epidermis. We show that autophagy is constitutively active in epidermal granular layer where by electron microscopy we identified double membrane-autophagosomes. We demonstrate that differentiating keratinocytes undergo a selective form of nucleophagy characterized by accumulation of LC3/LAMP2/p62 positive autolysosomes. These perinuclear vesicles displayed positivity for histone interacting protein HP1α and localize in proximity with Lamin A and B1 accumulation, while in newborn mice and adult human skin we report LC3 puncta coincident with misshaped nuclei within the granular layer. This process relies on autophagy integrity as confirmed by lack of nucleophagy in differentiating keratinocytes depleted from WIPI1 or ULK1. Final validation into a skin disease model showed that impaired autophagy contributes to the pathogenesis of psoriasis. Lack of LC3 expression in psoriatic skin lesions correlates with parakeratosis and deregulated expression or location of most of the autophagic markers. Our findings may have implications and improve treatment options for patients with epidermal barrier defects.
| Type: | Article |
|---|---|
| Title: | Constitutive autophagy and nucleophagy during epidermal differentiation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jid.2016.03.016 |
| Publisher version: | http://dx.doi.org/10.1016/j.jid.2016.03.016 |
| Language: | English |
| Additional information: | © 2016 Elsevier B.V. This manuscript is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher. |
| Keywords: | Autophagy, epidermal development, nucleophagy, terminal differentiation |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1485821 |
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