Melanin Transfer

Melanin transfer describes the transport of melanin-halitic melanosomes from melanocytes to keratinocytes. Melanosomes are considered LROs (lipid raft organelles) because they share proteins with lysosomes, are acidic in early stages and are secreted by melanocytes. Melanin synthesis and melanosome transport within melanocytes are well studied. The biogenesis of melanosomes is divided into four organelle stages. In stage I, non-pigmented pre-melanosomes form with internal membranous vesicles that resemble early/sorting endosomes. This compartment is characterized by intraluminal proteinaceous fibrils that begin to form in this stage and are completed in stage II. Melanin synthesis and maturation of melanosomes begin with the adoption of an elliptical shape at the end of stage II. Stage III is characterized by the deposition of melanin on the amyloid fibrils, leading to their thickening and darkening until they are fully melanized and reach stage IV, when they are considered fully mature melanosomes.

In order to be transferred to keratinocytes, melanosomes must be transported from the perinuclear region to the melanocyte dendrites. This is thought to occur in a two-step cooperative process in which melanosomes first utilize a microtubule-dependent bidirectional long-distance transport. In fact, melanosomes move in a kinesin 2-dependent manner to the cell periphery, where they are tethered to the actin cytoskeleton. At the periphery, melanosomes exhibit short-distance movement on the cortical actin network, which depends on the tripartite complex of myosin Va, melanophilin and Rab27a (Hume AN et al. 2007; Nagashima K et al. 2002). The RAB27A protein belongs to the superfamily of small GTPases, the Rab protein family. The protein is membrane-bound and may be involved in protein transport and signal transduction mediated by small GTPases. It is assumed that the distribution of melanosomes in melanocytes results from a competition between microtubule- and actin-dependent transport (Gross SP et al. 2002). Repulsion between melanosomes based on actin filament dynamics could potentially maintain the spread of melanosomes throughout the cytoplasm without the need for microtubule-dependent transport (Alzahofi N et al. 2020).

In cells of the retinal pigment epithelium (RPE), microtubule transport is essential for the rapid long-distance transport of melanosomes. Cytoplasmic dynein is equally essential for the transition of these organelles to actin filament-dependent transport (Jiang M et al. (2020).

The molecular mechanisms that control melanin transfer from melanocytes to keratinocytes remain controversial, as there is still no consensus in this area. There are currently four models to explain this process (Bento-Lopes L et al. 2023):

• (a) Cytophagocytosis of melanocyte third tips by keratinocytes;
• (b) direct membrane fusion between melanocytes and keratinocytes, resulting in filopodia through which melanosomes are transferred;
• (c) transfer of melanosome-laden vesicles from melanocytes, followed by internalization by keratinocytes
• (d) exocytosis of the melanin nucleus by melanocytes and subsequent internalization by keratinocytes

1. Alzahofi N et al. (2020) Rab27a Co-Ordinates Actin-Dependent Transport by Controlling Organelle-Associated Motors and Track Assembly Proteins. Nat. Commun11:3495).
2. Bento-Lopes L et al. (2023) Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing. Int J Mol Sci 24:11289.
3. Gross SP et al. (2002) Interactions and Regulation of Molecular Motors in Xenopus Melanophores. J Cell Biol 156:855-865)
4. Hume AN et al. (2007) Rab27a and MyoVa Are the Primary Mlph Interactors Regulating Melanosome Transport in Melanocytes. J Cell Sci 120:3111-3122
5. Hurbain I et al. (2018) Melanosome Distribution in Keratinocytes in Different Skin Types: Melanosome Clusters Are Not Degradative Organelles. J Investig Dermatol 138:647-656.
6. Jiang M et al. (2020) Microtubule Motor Transport in the Delivery of Melanosomes to the Actin-Rich Apical Domain of the Retinal Pigment Epithelium. J Cell Sci 133).
7. Nagashima K et al. (2002) Melanophilin Directly Links Rab27a and Myosin Va through Its Distinct Coiled-Coil Regions. FEBS Lett 517:233-238).