Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
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DOI：
10.1093/hmg/ddg320
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发表时间：
2003-11-15
影响因子：
3.5
通讯作者：
Hohl, D
中科院分区：
文献类型：
--
作者：
Chimienti, F;Hogg, RC;Hohl, D
malde Meleda是一种常染色体隐性炎症性和角化性掌跖皮肤疾病，由编码SLURP-1（哺乳动物分泌的Ly-6/ upar相关蛋白1）的ARS B基因突变引起。SLURP-1属于受体和分泌蛋白的Ly-6/uPAR超家族，参与信号转导、免疫细胞活化或细胞粘附。SLURP-1与蛇神经毒素和Lynx1的三指基序结构高度相似，表明该蛋白与神经元乙酰胆碱受体相互作用。我们发现SLURP-1增强了存在于角质形成细胞中的人α - 7烟碱乙酰胆碱受体。这些结果表明，SLURP-1是一种分泌的表皮神经调节剂，可能对伤口愈合过程中表皮稳态和抑制巨噬细胞释放tnf - α至关重要。这就解释了马尔·德·梅丽达的增生性和炎性临床表型。
Mal de Meleda is an autosomal recessive inflammatory and keratotic palmoplantar skin disorder due to mutations in the ARS B gene, encoding for SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1). SLURP-1 belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins, which participate in signal transduction, immune cell activation or cellular adhesion. The high degree of structural similarity between SLURP-1 and the three fingers motif of snake neurotoxins and Lynx1 suggests that this protein interacts with the neuronal acetylcholine receptors. We found that SLURP-1 potentiates the human alpha7 nicotinic acetylcholine receptors that are present in keratinocytes. These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing. This explains both the hyperproliferative as well as the inflammatory clinical phenotype of Mal de Meleda.