%0 Journal Article
%T DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.
%A Rathod M
%A Franz H
%A Beyersdorfer V
%A Wanuske MT
%A Leal-Fischer K
%A Hanns P
%A Stüdle C
%A Zimmermann A
%A Buczak K
%A Schinner C
%A Spindler V
%J J Cell Biol
%V 223
%N 4
%D 2024 04 1
%M 38477878
%F 8.077
%R 10.1083/jcb.202305006
%X 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.