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

Nature Communications
Lia DominguesCédric Delevoye

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.

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Citations

Oct 23, 2020·The Journal of Membrane Biology·Natasha BuwaNagaraj Balasubramanian
Nov 15, 2020·Current Opinion in Cell Biology·Miguel A Del PozoAsier Echarri
Mar 12, 2021·Frontiers in Cell and Developmental Biology·Claudia Matthaeus, Justin W Taraska
May 1, 2021·International Journal of Molecular Sciences·Hugo MoreirasDuarte C Barral
May 23, 2021·Integrative and Comparative Biology·Silvia Benito-MartínezCédric Delevoye

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Methods Mentioned

BETA
GTPases
electron tomography
transmission electron microscopy
ELISA
FCS
Protein Assay
PCR

Software Mentioned

ITEM
eTomo
MetaMorph
NIS
GraphPad Prism
softWorx
ImageJ
EMSIS
IMOD
Elements

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