DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.

Autor:	Rathod M; Department of Biomedicine, University of Basel, Basel, Switzerland.; Institute of Anatomy and Experimental Morphology, University Clinic Hamburg-Eppendorf , Hamburg, Germany., Franz H; Department of Biomedicine, University of Basel, Basel, Switzerland., Beyersdorfer V; Department of Biomedicine, University of Basel, Basel, Switzerland.; Institute of Anatomy and Experimental Morphology, University Clinic Hamburg-Eppendorf , Hamburg, Germany., Wanuske MT; Department of Biomedicine, University of Basel, Basel, Switzerland., Leal-Fischer K; Department of Biomedicine, University of Basel, Basel, Switzerland., Hanns P; Department of Biomedicine, University of Basel, Basel, Switzerland., Stüdle C; Department of Biomedicine, University of Basel, Basel, Switzerland., Zimmermann A; Department of Biomedicine, University of Basel, Basel, Switzerland., Buczak K; Proteomics Core Facility, Biocentre, University of Basel , Basel, Switzerland., Schinner C; Department of Biomedicine, University of Basel, Basel, Switzerland.; Institute of Functional and Applied Anatomy, Hannover Medical School , Hannover, Germany., Spindler V; Department of Biomedicine, University of Basel, Basel, Switzerland.; Institute of Anatomy and Experimental Morphology, University Clinic Hamburg-Eppendorf , Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Apr 01; Vol. 223 (4). Date of Electronic Publication: 2024 Mar 13.
DOI:	10.1083/jcb.202305006
Abstrakt:	Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes. In a 3D organotypic human epidermis model, loss of DPM1 caused impaired differentiation with abnormally increased cornification, reduced thickness of non-corneal layers, and formation of intercellular gaps in the epidermis. Using proteomic approaches, SERPINB5 was identified as a DPM1-dependent interaction partner of desmoplakin. Mechanistically, SERPINB5 reduced desmoplakin phosphorylation at serine 176, which was required for strong intercellular adhesion. These results uncover a novel role of the DPM complex in connecting desmosomal adhesion with epidermal differentiation. (© 2024 Rathod et al.)
Databáze:	MEDLINE
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