Influence of α‐melanocyte‐stimulating hormone and of ultraviolet radiation on the transfer of melanosomes to keratinocytes

Abstract

The epidermal melanin unit in human skin is composed of melanocytes and keratinocytes. Melanocytes, located in the basal layer of the epidermis, manufacture melanin-loaded organelles called melanosomes. Through their dendritic processes, melanocytes distribute melanosomes to neighboring keratinocytes, where their presence confers to the skin its characteristic color and photoprotective properties. In this study, we used murine melanocytes and keratinocytes alone and in coculture to characterize the processes involved in melanosome transfer. Ultraviolet (UV) radiation induced an accumulation of melanosomes in melanocytes, whereas treatment with a-melanocyte-stimulating hormone (MSH) induced exocytosis of melanosomes accompanied by ruffling of the melanocyte membrane. We found that keratinocytes phagocytose melanosomes and latex beads equally well and that this phagocytic process was increased by exposure of keratinocytes to UV radiation or to MSH. Coculture of melanocytes and keratinocytes resulted in an increase in MSH released to the medium. Gene array analysis of MSH-treated melanocytes showed up-regulation of many genes associated with exocytosis. In our studies, we never observed cytophagocytosis of melanosome-filled processes. This result, together with the other findings, suggests that a combination of signals that increase melanosome production and release by melanocytes and that stimulate phagocytosis by keratinocytes are the most relevant mechanisms involved in skin tanning.

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

“…␣-MSH and UV radiation are well known as major physiological signals that modulate skin pigmentation [1,22]. Melanocytes react to these signals by proliferation, increased dendriticity and elevated pigment synthesis.…”

Bone morphogenetic proteins differentially regulate pigmentation in human skin cells

“…Physiological factors such as pro-opiomelanocortin-derived peptides (e.g. a-MSH) (Virador et al, 2002) have been implicated. Here we for the first time showed that melanin transfer and filopodia formation can be markedly stimulated by BMP6 incubation in fully-matched MC-KC co-cultures.…”

“…However, just how melanin is transferred to neighbouring KCs has remained stubbornly enigmatic (Van Den Bossche et al, 2006). Several hypotheses have been proposed including: (i) cytophagocytosis of MC dendrite tips (Seiberg et al, 2000), (ii) exocytosis of melanosomes and subsequent uptake via phagocytosis into KC (Marks and Seabra, 2001;Virador et al, 2002) and (iii) filopodia-mediated melanosome transfer (Singh et al, 2010;Singh et al, 2008;Beaumont et al, 2011;Zhang et al, 2004;Scott et al, 2002). The role of filopodia in the transfer of melanosomes to keratinocytes was originally proposed by Scott and colleagues (Scott et al, 2002), and we extended this further in our recent report that proposed a 'filopodial-phagocytosis model' for melanin transfer (Singh et al, 2010).…”

Macelignan Inhibits Melanosome Transfer Mediated by Protease-Activated Receptor-2 in Keratinocytes

“…10) Skin pigment disorders such as melasma and postinflammatory hyperpigmentation are characterized by increased melanosome production and accumulation. 11) Hyperpigmentation has psychosocial and cosmetic relevance; therefore, considerable effort has been devoted to screening effective depigmenting agents. The ideal depigmenting agent exerts rapid, potent, and selective bleaching effects on melanocytes, has no side-effects, and permanently removes undesired pigment.…”