PDF(Pubmed)
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.
摘要：
糖基化是促进细胞-细胞粘附和分化所必需的。我们确定了磷酸多糖甘露糖基转移酶（DPM）复合物的作用，糖基化的中央调节剂，用于桥粒粘附功能和表皮分化。删除DPM复合物的关键分子，DPM1在人角质形成细胞中导致细胞-细胞粘附减弱，桥粒成分desmoplakin和desmoglein-2的定位受损，并导致人角质形成细胞的细胞骨架组织缺陷。在3D器官型人类表皮模型中，DPM1的缺失导致分化受损，角质化异常增加，减少非角膜层的厚度，并在表皮中形成细胞间间隙。使用蛋白质组学方法，SERPINB5被鉴定为desmoplakin的DPM1依赖性相互作用伴侣。机械上,SERPINB5减少了丝氨酸176处的desmoplakin磷酸化，这是强烈的细胞间粘附所必需的。这些结果揭示了DPM复合物在连接桥粒粘附与表皮分化中的新作用。
