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bioRxiv · 10.1101/2022.12.28.522133

Desmosomal cell cohesion and epidermal differentiation are modulated by dolichol phosphate mannosyltransferase 1 (DPM1) through SERPINB5-dependent mechanisms

Rathod, M.·Franz, H.·Beyersdorfer, V.·Wanuske, M.-T.·Fischer, K. L.·Stüdle, C.·Zimmermann, A.·Spindler, V.
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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 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 linking desmosomal adhesion with epidermal differentiation.

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Rathod, M., Franz, H., Beyersdorfer, V., Wanuske, M.-T., Fischer, K. L., Stüdle, C., Zimmermann, A., Spindler, V.. 2022-12-29. Desmosomal cell cohesion and epidermal differentiation are modulated by dolichol phosphate mannosyltransferase 1 (DPM1) through SERPINB5-dependent mechanisms. https://doi.org/10.1101/2022.12.28.522133

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