Abstract
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.
Highlights
Tissue homeostasis requires regulation of cell–cell communication, which relies on signaling molecules and cell contacts
This shows that the intrinsic asymmetry of caveolae in melanocytes is enhanced by keratinocytes, either by cell–cell contacts and/or by keratinocytes-secreted factors
The proportion of melanocytes with caveolae asymmetrically distributed was similar between cells co-cultured with keratinocytes (Fig. 1c) and cells incubated with keratinocyte-conditioned media (Ker-CM) (Fig. 1d), indicating that factors secreted from keratinocytes are the main extracellular contributors to the increased asymmetric distribution of caveolae in melanocytes
Summary
Tissue homeostasis requires regulation of cell–cell communication, which relies on signaling molecules and cell contacts. 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. The epidermis, the outermost and photoprotective layer of the skin, is mainly composed of melanocytes and keratinocytes that together create a structural and functional epidermal unit[1]. The formation of dendrites, melanosome biogenesis, synthesis and transfer of melanin to keratinocytes is a tightly coordinated process under the control of UV radiations, keratinocytes-secreted factors (e.g. hormones) and secreted endosomal-derived vesicles called exosomes[6,7,8]. We have recently shown that specific miRNAs associated with exosomes released from keratinocyte modulate human melanocyte pigmentation by enhancing the expression of proteins associated with melanosome maturation and trafficking[8]. Caveolae are mainly composed of two groups of proteins, the caveolins (Cav1, -2 and -3)[17] and the more recently identified cavins (Cavin[1, 2, 3] and 4)[18]
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