Coupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation

Lia Domingues (1) , Ilse Hurbain (1, 2) , Floriane Gilles-Marsens (1, 3) , Julia Sirés-Campos (1) , Nathalie André (4) , Melissa Dewulf (5) , Maryse Romao (1, 2) , Christine Viaris de Lesegno (5) , Anne-Sophie Macé (2) , Cédric Blouin (5) , Christelle Guéré (4) , Katell Vié (4) , Graça Raposo (1, 2) , Christophe Lamaze (5) , Cédric Delevoye (1, 2)

1 Structure and Membrane Compartments [Paris]
2 PICT-IBiSA - BioImaging Cell and Tissue Core Facility
3 Génétique et Neurobiologie de C. Elegans [Lyon]
4 Laboratoire Clarins [Pontoise]
5 CBMCT - UMR 3666 / U1143 - Chimie biologique des membranes et ciblage thérapeutique

Tissue homeostasis requires regulation of cell-cell communication, which relies on signaling molecules and cell contacts. In skin epidermis, keratinocytes secrete factors transduced by melanocytes into signaling cues promoting their pigmentation and dendrite outgrowth, while melanocytes transfer melanin pigments to keratinocytes to convey skin photoprotection. How epidermal cells integrate these functions remains poorly characterized. Here, we show that caveolae are asymmetrically distributed in melanocytes and particularly abundant at the melanocyte-keratinocyte interface in epidermis. Caveolae in melanocytes are modulated by ultraviolet radiations and keratinocytes-released factors, like miRNAs. Preventing caveolae formation in melanocytes increases melanin pigment synthesis through upregulation of cAMP signaling and decreases cell protrusions, cell-cell contacts, pigment transfer and epidermis pigmentation. Altogether, we identify that caveolae serve as molecular hubs that couple signaling outputs from keratinocytes to mechanical plasticity of pigment cells. The coordination of intercellular communication and contacts by caveolae is thus crucial to skin pigmentation and tissue homeostasis.

Domaines: Biologie cellulaire

Lia Domingues, Ilse Hurbain, Floriane Gilles-Marsens, Julia Sirés-Campos, Nathalie André, et al.. Coupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation. Nature Communications, 2020, 11 (1), pp.2988. ⟨10.1038/s41467-020-16738-z⟩. ⟨inserm-02877916⟩