Abstract
Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.
Highlights
Melanin determines colors of our skin, eyes, and hair and protects the skin from sunlight exposure
Our preliminary studies indicated that the interaction of tyrosinase with both adaptor-related protein (AP)-1 and AP-3 is likely to be involved in its transport to pre-formed immature stage II melanosomes
Primary melanocytes from a patient with Hermansky–Pudlak syndrome type 2, which have a mutation in an AP-3 subunit (Table 1), were compared with normal melanocytes to show that AP-3 transfers tyrosinase to melanosomes [62]
Summary
Melanin determines colors of our skin, eyes, and hair and protects the skin from sunlight exposure. MITF activates expression of key melanin-forming genes including genes for tyrosinase family enzymes and the melanosomal structural matrix protein PMEL. Small molecular materials that may be directly or indirectly involved in melanogenesis accumulate on the cell surface of melanocytes and are endocytosed through vesicular transport to melanosomal compartments [5]. This review discusses certain aspects of current progresses in major pathways of melanogenesis cascade which include (1) melanocyte development and differentiation, (2) melanosome biosynthesis and intracellular trafficking, and (3) melanin pigment-type switching, and introduces the possibility of applying the knowledge of melanogenesis cascade for elucidating the pathophysiology of pigmentary disorders and developing a novel therapeutic approach for malignant neoplasia of melanocytes, melanoma [12]
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