{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rathod M"],"funding":["Swiss National Science Foundation","Olga Mayenfisch Stiftung","Swiss Heart Foundation","Novartis Foundation for Medical-Biological Research"],"pagination":["e202305006"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10937187"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["223(4)"],"pubmed_abstract":["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."],"journal":["The Journal of cell biology"],"pubmed_title":["DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5."],"pmcid":["PMC10937187"],"funding_grant_id":["197764","22B086","FF21098"],"pubmed_authors":["Beyersdorfer V","Leal-Fischer K","Zimmermann A","Schinner C","Hanns P","Spindler V","Studle C","Buczak K","Wanuske MT","Rathod M","Franz H"],"additional_accession":[]},"is_claimable":false,"name":"DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2025-04-04T20:24:49.803Z","creation":"2025-04-04T20:24:49.803Z"},"accession":"S-EPMC10937187","cross_references":{"pubmed":["38477878"],"doi":["10.1083/jcb.202305006"]}}