RESEARCH ARTICLE


Cholesterol and Lipid Rafts as Regulators of Signaling Through the EGF Receptor in Keratinocytes



Sylviane Lambert1, Robert Gniadecki2, Yves Poumay*, 1
1 Cell and Tissue Laboratory, URPHYM, University of Namur (FUNDP), Namur, Belgium
2 Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen NV, Denmark


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© 2009 Lambert et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Cell & Tissue Laboratory, URPHYM, University of Namur (FUNDP), 61, rue de Bruxelles, B-5000 Namur, Belgium; Tel: +32-81-724257; Fax: +32-81-724261; E-mail:yves.poumay@fundp.ac.be


Abstract

The EGF receptor (HER1/EGFR) and its cognate ligands are of considerable interest in epidermal biology and pathology. HER1/EGFR is expressed throughout the entire epidermis and its signaling has been shown involved in the control of keratinocyte proliferation, adhesion, and differentiation. The signaling of HER1/EGFR can be modulated by the receptor’s immediate environment, particularly by its localization or not in lipid rafts. These membrane domains are nowadays described as heterogeneous dynamic signaling platforms where lipid molecules, cholesterol especially, are highly ordered and where transmembrane proteins encounter a specialized environment. Cholesterol depletion has been used in order to disorganize lipid rafts in keratinocytes and induces activation of HER1/EGFR (without ligand addition), as well as downstream signaling. The activation of p38 MAPK obtained after cholesterol depletion is responsible for the induction of involucrin expression while keratin expression is suppressed. However in keratinocytes recovering from cholesterol depletion the activation of p38 MAPK induces a strong expression of the heparin-binding EGF-like growth factor, a ligand of HER1/EGFR. Lipid rafts could thus be membrane platforms that regulate cell signaling in keratinocytes in normal, but also pathological conditions.