Melanosome transport and regulation in development and disease
Introduction
Melanosomes are organelles that are responsible for the synthesis, storage and transport of melanin, the most common light-absorbing pigment. These large lysosome-related organelles (~500 nm diameter) are bound by a bilipid membrane and are generally rounded, sausage-like, or cigar-like in shape. Due to their dark pigment, melanosomes are easily visible through bright-field microscopy; a melanosome’s visibility varies with its maturity and this technique can be used to categorize melanosomes under a numeric staging system. Usually, melanosomes are divided into four stages according to morphology. Non-pigmented stage I vacuoles, which are derived from endosomal systems alone, acquire internal striations to form stage II melanosomes. Melanin synthesis and accumulation in these striations begin in stage III; these melanosomes eventually mature into the fully melanized stage IV form (Raposo & Marks, 2007) (Fig. 1).
Section snippets
Skin pigmentation in different races
Skin color is mainly determined by the content and composition of melanin in the epidermis (Alaluf et al., 2002; Jimbow, Quevedo, Fitzpatrick, & Szabo, 1976). While the number of melanocytes remains relatively consistent among different races at approximately 1000 melanocytes per mm2 (a 1:36 melanocyte to keratinocyte ratio) (Staricco & Pinkus, 1957), the size, packaging and distribution of melanosomes vary significantly (Fig. 2). However, there are reports that show higher numbers of
Membrane transport
The identification of melanosome-membrane transport machinery largely benefits from research concerning the HPS disease. So far 10 genes, namely HPS1–10, that encode the subunits of the lysosome-related organelle complex (BLOC)-1, -2, -3, and adaptor protein-3 (AP-3) in biogenesis, have been identified to cause HPS in humans (Fig. 3); this autosomal recessive disorder is characterized by hypopigmentation, loss of visual acuity, and bleeding tendency, colitis, or fetal lung disease (Ammann et
Endocrine hormones
Besides the well-established role of α-MSH in melanogenesis, other hormones are also involved in this process. For fishes and amphibians, hormones such as melanin concentrating hormone (MCH) (Logan, Burn, & Jackson, 2006), thyroid hormone (McMenamin et al., 2014; Saunders et al., 2019), thyrotropin-releasing hormone (TRH) (Jackson & Reichlin, 1977) and insulin (Y. M. Zhang et al., 2018), regulate pigment patterning by modulating melanosome dispersion or melanophore proliferation and
Vitiligo
Vitiligo is a chronic depigmenting disease that originates from the loss of melanocytes in the skin; the cause of this disease remains controversial (Picardo et al., 2015). In the melanocyte of both in vivo biopsy and the long-term cultured melanocyte from vitiligo patient, there is an obvious dilation of the rough ER, an appearance of circular rough ER profiles, and a disruption in the mitochondria (Boissy, Beato, & Nordlund, 1991a; Boissy, Liu, Medrano, & Nordlund, 1991b). In the long-term
Conclusions and perspectives
Melanosomes protect human health, and defects in melanosome regulation lead to pigmentation disorders and associated diseases with negative effects on human lives. Information has been obtained regarding the molecular mechanisms underlying melanosome transfer and genesis, paving the way for new practical therapies for melanosome-related diseases.
However, many questions remain. How do microtubules cooperate with actin filaments for melanosome transport? How is the directionality of melanosome
Declaration of Competing Interest
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was supported by the Taishan Scholars Program of Shandong Province (20161201).
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