Advances in melanocyte basic science research

The epidermal melanin system has been the interest of intense research for many decades. The pigment-forming cell, which is the neural crest-derived melanocyte, produces melanin in small unique organelles, the melanosomes, which contain the enzyme tyrosinase (EC 1.14.18.1) to initiate melanogenesis from L-tyrosine. Melanocytes are true secretory cells because the melanosomes are transferred or secreted to the Surrounding keratinocytes. Both cells interact closely Lis a structural and functional unit, which consequently was named the epidermal unit. It was documented that one melanocyte is surrounded by 36 keratinocytes [1]. The main function of melanocytes resides in the formation of melanins, which form the basis for skin, hair, and eye color and offer an efficient free radical scavenger and ultraviolet (UV) filter. Research on the biochemistry of melanogenesis started with the discovery of the enzyme tyrosinase in mushrooms in 1895 by Bertrand and Bourquelot. In 1917, Bloch showed dopa oxidase activity in human skin, and Raper (1927) elicited the first chemical steps in the conversion of tyrosine to melanin in 1920. In 1928, he showed that L-DOPA was the oxidation product from L-tyrosine itself [2]. In 1942, Hogeboom and Adams [3] demonstrated the first mammalian tyrosinase in the Harding-Passay melanoma, and they proposed a two-enzyme hypothesis for the formation of melanin. Lerner and colleagues [4] were unable to separate tyrosinase activity from dopa oxidase activity. There has been some controversy since that time. Even to date, however, most pigment cell biologists believe that a single enzyme is involved in the oxidation of tyrosine to melanin. Advances in understanding the physiology and pathophysiology of the pigmentation process have been made over the last few decades. Several cytokines and growth factors have been established to Support the transformation of migrating melanoblasts to differentiated functional melanocytes. Research showed that mast cell growth factor (c-kit) is a major player in the migration of melanoblasts from the neural crest to its final destination. Endothelin-1 has been implicated in adhesion and differentiation, and the melanocortins (eg, adrenocorticotropic hormone (ACTH), alpha-melanocyte Stimulating hormone (alpha-MSH), and beta-endorphin) and recently beta-MSH and cate-cholamines, acetylcholine, and estrogens with their specific receptors have been invoked in melanocyte function. The IP3/DAG/PKC beta signal transduction systems have been shown to be involved [5-8]. The cofactor (6R)-L-erythro- 5,6,7,8-terahydrobiopterin (6BH(4)) and its 7-isomer were recognized as important in the regulation of pigmentation [9]. Production of melanins (ie, eumelanin [brown/black] and pheomelanin [yellow/red]) occurs in a specialized lysosome-derived organelle in which number and maturation of those per melanocyte determine skin color [10,11]. This article focuses on newer aspects of melanocyte biology and biochemistry.