DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5
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DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5. / Rathod, Maitreyi; Franz, Henriette; Beyersdorfer, Vivien; Wanuske, Marie-Therès; Fischer, Karen Leal; Hanns, Pauline; Stüdle, Chiara; Zimmermann, Aude; Buczak, Katarzyna; Schinner, Camilla; Spindler, Volker.
In: J CELL BIOL, Vol. 223, No. 4, 01.04.2024, p. e202305006.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5
AU - Rathod, Maitreyi
AU - Franz, Henriette
AU - Beyersdorfer, Vivien
AU - Wanuske, Marie-Therès
AU - Fischer, Karen Leal
AU - Hanns, Pauline
AU - Stüdle, Chiara
AU - Zimmermann, Aude
AU - Buczak, Katarzyna
AU - Schinner, Camilla
AU - Spindler, Volker
N1 - © 2024 Rathod et al.
PY - 2024/4/1
Y1 - 2024/4/1
N2 - 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.
AB - 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.
KW - Humans
KW - Desmoplakins
KW - Proteomics
KW - Cell Differentiation
KW - Keratinocytes
KW - Cell Adhesion
KW - Dolichols
KW - Phosphates
U2 - 10.1083/jcb.202305006
DO - 10.1083/jcb.202305006
M3 - SCORING: Journal article
C2 - 38477878
VL - 223
SP - e202305006
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 4
ER -
