PDF(Pubmed)
Abstract：
Among the 33 human adhesion G-protein-coupled receptors (aGPCRs), a unique subfamily of GPCRs, only ADGRF4, encoding GPR115, shows an obvious skin-dominated transcriptomic profile, but its expression and function in skin is largely unknown. Here, we report that GPR115 is present in a small subset of basal and in most suprabasal, noncornified keratinocytes of the stratified epidermis, supporting epidermal transcriptomic data. In psoriatic skin, characterized by hyperproliferation and delayed differentiation, the expression of GPR115 and KRT1/10, the fundamental suprabasal keratin dimer, is delayed. The deletion of ADGRF4 in HaCaT keratinocytes grown in an organotypic mode abrogates KRT1 and reduces keratinocyte stratification, indicating a role of GPR115 in epidermal differentiation. Unexpectedly, endogenous GPR115, which is not glycosylated and is likely not proteolytically processed, localizes intracellularly along KRT1/10-positive keratin filaments in a regular pattern. Our data demonstrate a hitherto unknown function of GPR115 in the regulation of epidermal differentiation and KRT1.
摘要：
在33种人粘附G蛋白偶联受体（aGPCRs）中，一个独特的GPCRs亚家族,只有编码GPR115的ADGRF4显示出明显的皮肤主导转录组特征，但其在皮肤中的表达和功能在很大程度上是未知的。这里,我们报告GPR115存在于基底的一小部分和大多数基底上，分层表皮的非角化角质形成细胞，支持表皮转录组数据。在牛皮癣皮肤中，以过度增殖和延迟分化为特征，GPR115和KRT1/10的表达，基本的基底上角蛋白二聚体，被延迟了。以器官型模式生长的HaCaT角质形成细胞中ADGRF4的缺失消除了KRT1并减少了角质形成细胞分层，表明GPR115在表皮分化中的作用。出乎意料的是,内源性GPR115，它不是糖基化的，很可能不是蛋白水解加工的，沿KRT1/10阳性角蛋白丝以规则的方式在细胞内定位。我们的数据表明，GPR115在调节表皮分化和KRT1方面具有迄今为止未知的功能。
