Melanosomes Are Transferred from Melanocytes to Keratinocytes through the Processes of Packaging, Release, Uptake, and Dispersion

Abstract

Recent studies have described the role of shedding vesicles as physiological conveyers of intracellular components between neighboring cells. Here we report that melanosomes are one example of shedding vesicle cargo, but are processed by a previously unreported mechanism. Pigment globules were observed to be connected to the filopodia of melanocyte dendrites, which have previously been shown to be conduits for melanosomes. Pigment globules containing multiple melanosomes were released from various areas of the dendrites of normal human melanocytes derived from darkly pigmented skin. The globules were then captured by the microvilli of normal human keratinocytes, also derived from darkly pigmented skin, which incorporated them in a protease-activated receptor-2 (PAR-2)-dependent manner. After the pigment globules were ingested by the keratinocytes, the membrane that surrounded each melanosome cluster was gradually degraded, and the individual melanosomes then spread into the cytosol and were distributed primarily in the perinuclear area of each keratinocyte. These results suggest a melanosome transfer pathway wherein melanosomes are transferred from melanocytes to keratinocytes via the shedding vesicle system. This packaging system generates pigment globules containing multiple melanosomes in a unique manner.

Melanoregulin regulates a shedding mechanism that drives melanosome transfer from melanocytes to keratinocytes

“…Moreover, based solely on still images at the light and electron microscopy levels, they argue that these melanosome-rich packages are shed from the melanocyte's surface (16). Importantly, our dynamic imaging proves, in a way that their still images cannot, that this shedding is an active process involving contact between the melanocyte and the keratinocyte, thinning of the melanocyte's dendrite behind the region to be shed, and apparent self-abscission.…”

“…Importantly, our dynamic imaging proves, in a way that their still images cannot, that this shedding is an active process involving contact between the melanocyte and the keratinocyte, thinning of the melanocyte's dendrite behind the region to be shed, and apparent self-abscission. Moreover, in contrast to the static imaging performed by Ando et al (16) on pure melanocyte cultures, our union of both dynamic imaging and melanocyte/keratinocyte coculture provides important temporal and spatial information about the roles played by both cell types in the sequential steps driving transfer, including adhesion, dendrite thinning, abscission, and phagocytosis. Finally, the fact that Ando et al (16) used pure melanocyte cultures argues that the shedding of melanosome packages is (or at least can be) a purely melanocyte cell autonomous phenomena.…”

Keratinocyte-derived Laminin-332 Protein Promotes Melanin Synthesis via Regulation of Tyrosine Uptake

“…To serve a photoprotective role, melanin produced in melanocytes needs to transfer to neighbor keratinocytes, the predominant cell type in the skin epidermis, to protect keratinocytes from UV light (7). Therefore, keratinocytes are actively involved in the regulation of melanin synthesis.…”

Crosstalk in skin: melanocytes, keratinocytes, stem cells, and melanoma

“…Each melanocyte is in contact with 30-40 neighboring keratinocytes through long dendritic extensions that form adhesive structures (Fitzpatrick and Breathnach 1963). Melanosomes, the pigment-containing unit, are produced in melanocytes and passed on to keratinocytes where they affect skin pigmentation and protection against UV radiation (Ando et al 2012). Consequently, the cell-cell interactions provide the opportunity for crosstalk between keratinocytes and melanocytes and for the skin microenvironment to adapt in response to external stimuli.…”