title: Rab11a Is Essential for Lamellar Body Biogenesis in the Human Epidermis.
abstract: Most of the skin barrier function is attributable to the outermost layer of the epidermis, the stratum corneum, which is composed of flattened, anucleated cells called corneocytes surrounded by a lipid-enriched lamellar matrix. The composition of the stratum corneum is directly dependent on the underlying granular keratinocytes, which are the last living cells in the stratified epidermis. Many components present in the intercorneocyte matrix are delivered by the underlying granular keratinocytes through a secretion process dependent on lysosome-related organelles called lamellar bodies. Because of the importance of lamellar bodies in the maintenance of the epidermal barrier, the mechanisms regulating their biogenesis must be better understood. In this study, we show that the Rab11a GTPase is highly expressed in terminally differentiated keratinocytes, where it is partly associated with lamellar bodies. Rab11a silencing in three-dimensional in vitro reconstructed human epidermis induces a barrier defect, a decrease in the amount of lipid found in the stratum corneum, a reduction in lamellar body density and secretion areas in granular keratinocytes, and the mis-sorting of lamellar body cargoes being driven to the lysosomal degradation pathway. Our results highlight the importance of Rab11a-dependent regulation of lamellar body biogenesis in keratinocytes and consequently on epidermal barrier homeostasis.
authors.affiliation: UDEAR UMR 1056 Institut National de la Santé et de la Recherche Médicale, 31059 Toulouse, France; University of Toulouse, 31059 Toulouse, France; FRE 3742 Centre National de la Recherche Scientifique, 31059 Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Reynier
authors.affiliation: UMR 1043 Institut National de la Santé Et de la Recherche Médicale, TRI Genotoul, 31059 Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Allart
authors.affiliation: UDEAR UMR 1056 Institut National de la Santé et de la Recherche Médicale, 31059 Toulouse, France; University of Toulouse, 31059 Toulouse, France; FRE 3742 Centre National de la Recherche Scientifique, 31059 Toulouse, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Gaspard
authors.affiliation: SYNELVIA, 31670 Labège, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Moga
authors.affiliation: Centre de Microscopie Electronique Appliquée à la Biologie (CMEAB), Faculté de Médecine Rangueil, University of Toulouse, 31062 Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Goudounèche
authors.affiliation: UDEAR UMR 1056 Institut National de la Santé et de la Recherche Médicale, 31059 Toulouse, France; University of Toulouse, 31059 Toulouse, France; FRE 3742 Centre National de la Recherche Scientifique, 31059 Toulouse, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.affiliation: UDEAR UMR 1056 Institut National de la Santé et de la Recherche Médicale, 31059 Toulouse, France; University of Toulouse, 31059 Toulouse, France; FRE 3742 Centre National de la Recherche Scientifique, 31059 Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
authors.affiliation: UDEAR UMR 1056 Institut National de la Santé et de la Recherche Médicale, 31059 Toulouse, France; University of Toulouse, 31059 Toulouse, France; FRE 3742 Centre National de la Recherche Scientifique, 31059 Toulouse, France. Electronic address: corinne.leprince@inserm.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leprince
mesh_terms: D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism*; D020868:Gene Silencing; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D001678:Organelle Biogenesis; D012494:Sampling Studies; D046509:Tissue Culture Techniques; D020691:rab GTP-Binding Proteins / Q000235:genetics*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins