Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

Abstract

The mechanisms by which the pigment melanin is transferred from melanocytes and processed within keratinocytes to achieve skin pigmentation remain ill-characterized. Nevertheless, several models have emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations in favor of the exo/phagocytosis and shed vesicles models. In order to reconcile the transfer models, we propose that different mechanisms could co-exist to sustain skin pigmentation under different conditions. We also discuss the limited knowledge about melanin processing within keratinocytes. Finally, we pinpoint new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications.

Rab3a regulates melanin exocytosis induced by keratinocyte-conditioned medium

“…Melanin transfer from melanocytes to keratinocytes is a crucial process for skin pigmentation and photoprotection against UVr-induced cell damage. Our previous studies suggested that coupled exo/phagocytosis is the predominant mechanism of melanin transfer in human skin and showed an essential role for Rab11b and the exocyst tethering complex in this process (Tarafder et al, 2014;Moreiras et al, 2019) 1( 1) . Here we provide evidence that the process of melanin exocytosis is more complex than previously appreciated and demonstrate the existence of at least two types of melanin exocytosis pathways, including a novel one induced by keratinocytes and regulated by the Rab3a small GTPase.…”

“…Finally, the coverslips were mounted with Fluoromount-G with DAPI (Invitrogen, Lenexa, Kansas) to visualize the cells' nuclei and images were acquired in a ZEISS Axio Imager 2 microscope with a PlanApochromat 63x1.4 NA oil-immersion objective. The melanin-containing organelles present within keratinocytes, which we proposed to call melanokerasomes (Moreiras et al, 2021b), were counted using ImageJ software and normalized to the number of cells analyzed in each image.…”

“…The mechanism of melanin transfer remains elusive. We propose that the predominant mode in human skin is coupled exo/phagocytosis (Tarafder et al, 2014;Moreiras et al, 2021b) (1) . Before melanin is transferred, melanosomes are transported to melanocyte dendrites, where they are tethered to the cortical actin cytoskeleton via the tripartite complex Rab27a/Melanophilin/Myosin Va (Barral and Seabra, 2004;Hume et al, 2007).…”

Computer-Aided Detection (CADe) System with Optical Coherent Tomography for Melanin Morphology Quantification in Melasma Patients

“…The compartment of melanin taken up by keratinocytes from melanocytes was recently given the name melanokerasome [7,8,[24][25][26][27]. Our previous study comparing hematoxylin and eosin (H&E) stain slice and OCT images revealed melanin appears as hyper-reflective cells with a relatively strong intensity compared with the surrounding tissues [6].…”

“…Studies suggested melanocytes rapidly transfer the produced melanin to keratinocytes rather than accumulating it [7]. This may explain that typical active dendritic melanocytes were hardly observed, while supranuclear melanin caps in the keratinocytes were easily visible [8,9]. Melanin amount and distribution are therefore commonly used to classify the melasma subtypes and to monitor the treatment response [10].…”