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      Recent advances in understanding the molecular basis of melanogenesis in melanocytes

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          Abstract

          Melanin pigments are responsible for human skin and hair color, and they protect the body from harmful ultraviolet light. The black and brown melanin pigments are synthesized in specialized lysosome-related organelles called melanosomes in melanocytes. Mature melanosomes are transported within melanocytes and transferred to adjacent keratinocytes, which constitute the principal part of human skin. The melanosomes are then deposited inside the keratinocytes and darken the skin (a process called tanning). Owing to their dark color, melanosomes can be seen easily with an ordinary light microscope, and melanosome research dates back approximately 150 years; since then, biochemical studies aimed at isolating and purifying melanosomes have been conducted. Moreover, in the last two decades, hundreds of molecules involved in regulating melanosomal functions have been identified by analyses of the genes of coat-color mutant animals and patients with genetic diseases characterized by pigment abnormalities, such as hypopigmentation. In recent years, dynamic analyses by more precise microscopic observations have revealed specific functions of a variety of molecules involved in melanogenesis. This review article focuses on the latest findings with regard to the steps (or mechanisms) involved in melanosome formation and transport of mature melanosomes within epidermal melanocytes. Finally, we will touch on current topics in melanosome research, particularly on the "melanosome transfer" and "post-transfer" steps, and discuss future directions in pigment research.

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          Most cited references36

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          Two newly identified genetic determinants of pigmentation in Europeans.

          We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.
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            The road to lysosome‐related organelles: Insights from Hermansky‐Pudlak syndrome and other rare diseases

            Lysosome-related organelles comprise a diverse group of cell type-specific, membrane-bound subcellular organelles that derive at least in part from the endolysosomal system but that have unique contents, morphology, and functions to support specific physiological roles. They include melanosomes that provide pigment to our eyes and skin, alpha and dense granules in platelets and lytic granules in cytotoxic T cells and natural killer cells that release effectors to regulate hemostasis and immunity, and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of lysosome-related organelles are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky-Pudlak syndromes. This review provides a comprehensive overview of lysosome-related organelles in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.
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              Melanosome transfer: it is best to give and receive.

              The pigmentation of skin and hair in mammals is driven by the creation within melanocytes of melanosomes, a specialized pigment-producing organelle, and the subsequent intercellular transfer of this organelle to keratinocytes. This latter process is absolutely required for visible pigmentation and effective photo-protection because it serves to disperse the pigment in skin and hair. Therefore, the transfer of melanosomes from the melanocyte to the keratinocyte is as important for the biological endpoint of mammalian pigmentation as the biogenesis of this fascinating organelle. Here we review new findings that shed light on, and raise additional questions about, the mechanism of this enigmatic process.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding AcquisitionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Funding AcquisitionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                15 June 2020
                2020
                : 9
                : F1000 Faculty Rev-608
                Affiliations
                [1 ]Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan
                [2 ]Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Miyagi 980-8578, Japan
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-8620-5853
                Article
                10.12688/f1000research.24625.1
                7308992
                f1ef1760-34ba-4a32-b740-1d3c86685f4d
                Copyright: © 2020 Ohbayashi N and Fukuda M

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 June 2020
                Funding
                Funded by: Ministry of Education, Culture, Sports, Science and Technology
                Award ID: 19K06653/19H03220
                Funded by: Japan Science and Technology Agency
                Award ID: JPMJCR17H4
                This work was supported in part by Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (grant number 19K06653 to N.O.), Grant-in-Aid for Scientific Research (B) from the MEXT (grant number 19H03220 to M.F.), and Japan Science and Technology Agency (JST) CREST (grant number JPMJCR17H4 to M.F.).
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                bloc,melanogenic enzymes,melanosome maturation,membrane traffic,rab small gtpase

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