小眼畸形相关转录因子
黑素细胞
生物
黑色素
白癜风
细胞生物学
人体皮肤
下调和上调
表皮(动物学)
转录组
表型
基因
受体
基因表达
黑色素瘤
免疫学
癌症研究
遗传学
解剖
转录因子
作者
Laura Sormani,Henri Montaudié,Lauriane Blot,Marjorie Heim,Nathalie Leccia,Rana Mhaidly,Els Verhoeyen,Claire Regazzetti,Nicolas Nottet,Yann Cheli,Gian Marco De Donatis,Anne Sophie Dabert Gay,Delphine Debayle,Helene A. Martin,Franck Gesbert,Stéphane Rocchi,Meri K. Tulic,Thierry Passeron
标识
DOI:10.1016/j.jid.2021.08.450
摘要
Pigmentation of the human skin is a complex process regulated by many genes. However, only a few have a profound impact on melanogenesis. Transcriptome analysis of pigmented skin compared with analysis of vitiligo skin devoid of melanocytes allowed us to unravel CLEC12B as a melanocytic gene. We showed that CLEC12B, a C-type lectin receptor, is highly expressed in melanocytes and that its expression is decreased in dark skin compared with that in white skin. CLEC12B directly recruits and activates SHP1 and SHP2 through its immunoreceptor tyrosine-based inhibitory motif domain and promotes CRE-binding protein degradation, leading to the downregulation of the downstream MITF pathway. CLEC12B ultimately controls melanin production and pigmentation in vitro and in a model of reconstructed human epidermis. The identification of CLEC12B in melanocytes shows that C-type lectin receptors exert function beyond immunity and inflammation. It also provides insights into the understanding of melanocyte biology and regulation of melanogenesis.
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