1. CLEC12B Is a Melanocytic Gene Regulating the Color of the Skin
- Author
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Laura Sormani, Henri Montaudie, Lauriane Blot, Marjorie Heim, Nathalie Cardot Leccia, Rana Mhaidly, Els Verhoeyen, Claire Regazzetti, Nicolas Nottet, Yann Cheli, Gian Marco De Donatis, Anne Sophie Dabert Gay, Delphine Debayle, Hélène Taquin Martin, Franck Gesbert, Stéphane Rocchi, Meri K. Tulic, and Thierry Passeron
- Subjects
Melanins ,Receptors, Mitogen ,Humans ,Melanocytes ,Lectins, C-Type ,Skin Pigmentation ,Cell Biology ,Dermatology ,Epidermis ,Molecular Biology ,Biochemistry ,Skin - Abstract
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.
- Published
- 2022
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