Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

Abstract

The mechanisms that regulate skin pigmentation have been the subject of intense research in recent decades. In contrast with melanin biogenesis and transport within melanocytes, little is known about how melanin is transferred and processed within keratinocytes. Several models have been proposed for how melanin is transferred, with strong evidence supporting coupled exo/endocytosis. Recently, two reports suggest that upon internalization, melanin is stored within keratinocytes in an arrested compartment, allowing the pigment to persist for long periods. In this commentary, we identify a striking parallelism between melanin processing within keratinocytes and the host-pathogen interaction with Plasmodium, opening new avenues to understand the complex molecular mechanisms that ensure skin pigmentation and photoprotection. K E Y W O R D S autophagy, endocytic pathway, melanin, membrane traffic, Plasmodium, UV-radiation 1 | SYNOPSIS Melanin processing within keratinocytes remains elusive. Recent reports suggest that melanin escapes degradation and remains in an arrested compartment inside keratinocytes for long periods. In this commentary, we highlight the similarities between melanin processing and the host-pathogen interaction that occurs with Plasmodium during liver infection and point out some of the most important questions yet to be answered. The skin is the largest organ of the human body and alongside its barrier properties against external aggressions, it has an important ultraviolet (UV)-protective function. The superficial layer, the epidermis is composed by two main cell types: keratinocytes and melanocytes. Keratinocytes form a stratified epithelium differentiating from the basal layer to the cornified superficial layers. Melanocytes are residents of the basal layer and are responsible for the synthesis, packaging and transfer of the pigment melanin to neighboring keratinocytes.Photoprotection is achieved by the polarization of melanin around the nucleus of keratinocytes, forming a supra-nuclear melanin cap or "parasol" on the sun-exposed side, effectively protecting the nuclear DNA from UV-induced damage. 1 Skin pigmentation is, therefore the result of a cross-talk between melanocytes and keratinocytes, where melanocytes are pigment-producers and keratinocytes are pigment- recipients. 2Melanosome biogenesis is initiated at the perinuclear region and undergoes a process of organelle maturation, whereas fully mature melanosomes tend to accumulate at the tips of melanocyte dendrites. 3 When fully mature and located at the tips of melanocyte dendrites, melanin is transferred to keratinocytes. The actual mechanism of melanin transfer remains controversial. Recently, we proposed that the predominant model of melanin transfer is coupled exo/endocytosis where the melanin core or "melanocore" is exocytosed by melanocytes and then internalized by keratinocytes. 4Regardless of the transfer mechanism, melanin is processed within keratinocytes and ends up forming a well-described supranuclear cap, polarized to the s...

A Melanin-Related Phenolic Polymer with Potent Photoprotective and Antioxidant Activities for Dermo-Cosmetic Applications

“…Low molecular weight components such as dimeric compounds were appreciably internalized after 1 h incubation. These data provide further confirmation to biological studies indicating that keratinocytes are able to internalize melanins as the result of a cross-talk with melanocytes, mediated by the protease-activated receptor 2 (PAR-2) and the Ras-related protein Rab11 [59,60]. Overall, our findings demonstrate that MeDHICA-melanin is able to enter the cells and activate the antioxidant system to protect skin cells from UVA-induced damage, encouraging its use as an effective component in dermo-cosmetic formulations for the treatment of skin damage, photoaging and skin cancers.…”

Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

“…Hence, the first task where this approach can find application is the investigation of melanin fate and its redistribution in the epidermis upon stress conditions such as UV exposure 2,68 , oxidative and mechanical stress 11 , etc. Although this task is seemingly simple, the fact is that a number of questions about the melanin fate (such as the presence of "melanin dust" in the stratum corneum 13,14 ), kinetics and mechanisms of its transfer in normal and stress conditions and the degradation pathways 7,[11][12][13][14] require additional studies, in which the suggested method could be useful.…”

“…However, in later works, autophagy was demonstrated not to have a substantial effect on skin pigmentation 9 , and melanosomes were shown to be non-degradative 10 . Other mechanisms like inherent asymmetric localization of melanosomes between dividing keratinocytes could be potentially involved in a complex inhomogeneous distribution of melanin in the epidermis [11][12][13] . Hence, precise assessment of melanin distribution in different epidermal layers is required to study fundamental processes and identify melanin-related abnormalities in norm and pathology.…”

Microtubule motor transport in the delivery of melanosomes to the actin-rich apical domain of the retinal pigment epithelium

“…Skin melanocytes and RPE cells are two mammalian cell types in which melanosomes move from the cell body to the cell periphery. In melanocytes, melanosome biogenesis is active (Raposo and Marks, 2007) and the melanosomes do not return to the cell body; they are delivered to keratinocytes from the melanocyte dendrites (Hume et al, 2001;Wasmeier et al, 2008;Fukuda, 2013;Wu and Hammer, 2014;Moreiras et al, 2019). By contrast, melanosome biogenesis is very low in the postnatal RPE (Lopes et al, 2007b).…”

“…In mammalian skin, melanosome biogenesis occurs in melanocytes (Raposo and Marks, 2007). The melanosomes then pass from the dendrites of the melanocytes to neighboring keratinocytes (Hume et al, 2001;Wasmeier et al, 2008;Fukuda, 2013;Wu and Hammer, 2014;Moreiras et al, 2019). Preceding the intercellular transfer, melanosomes must be transported and retained in the melanocyte dendrites.…”