{Reference Type}: Journal Article
{Title}: DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.
{Author}: Rathod M;Franz H;Beyersdorfer V;Wanuske MT;Leal-Fischer K;Hanns P;Stüdle C;Zimmermann A;Buczak K;Schinner C;Spindler V;
{Journal}: J Cell Biol
{Volume}: 223
{Issue}: 4
{Year}: 2024 04 1
{Factor}: 8.077
{DOI}: 10.1083/jcb.202305006
{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.