Fig. 2

Melanosome biogenesis, structure, functions and fate. (A) Schematic of melanosome biogenesis and maturation pathways. Melanogenic cargoes such as OCA2, MART-1 or TYR are transferred to maturing melanosomes through diverse trafficking pathways during melanogenesis. Melanosome maturation is influenced by pH and membrane contacts with other organelles including lysosomes. (B) Transmission electron micrograph of a melanocyte within the skin epidermis. The insets highlight examples of melanosomes at the different stages of maturation. PMEL fibrils are visible in stages II and III melanosomes before being buried under accumulating melanin pigments in stage IV melanosomes. (C) Schematic of the eumelanin and pheomelanin biosynthetic pathways in melanosomes. Several enzymes such as TYR, TYRP1 and DCT, and transporters including vATPase, TPC2 and ATP7A regulate melanogenesis through modulation of pH, membrane potential or ion content within melanosomes. (D) Schematic of the putative melanin transfer mechanisms occurring within the skin epidermis. Melanosomes are transported by kinesins across microtubules toward melanocyte dendrite tips (inset 1). Stage IV melanosomes are then trapped within actin fibers by a tripartite complex composed of Myosin Va, Melanophilin and Rab27a (inset 2). Melanin transfer could then result from filopodia nanotube formation (inset 3), cytophagosis of melanocyte dendrites (inset 4), vesicle transfer (inset 5) or exocytosis/endocytosis (inset 6). Within keratinocytes, melanin forms nuclear caps above cell nuclei to protect DNA from photodamage