DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.

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.

Citation

Maitreyi Rathod, Henriette Franz, Vivien Beyersdorfer, Marie-Therès Wanuske, Karen Leal-Fischer, Pauline Hanns, Chiara Stüdle, Aude Zimmermann, Katarzyna Buczak, Camilla Schinner, Volker Spindler. DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5. The Journal of cell biology. 2024 Apr 01;223(4)

Mesh Tags

Substances

PMID: 38477878

search → result