Abstract
Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.
Highlights
Cells release extracellular vesicles (EVs) from at least two different origins, namely exosomes and microvesicles
Melanocytes and melanoma cell lines have shown that UVA irradiation causes plasma membrane damage that is repaired through lysosomal exocytosis[8,9,10]
The number of melanocytes positive for lysosomal-associated membrane protein-1 (LAMP-1) at the plasma membrane was significantly lower under Ca2+-free conditions, confirming that the UVA-induced plasma membrane damage is repaired through lysosomal exocytosis (Fig. 1b)
Summary
Cells release extracellular vesicles (EVs) from at least two different origins, namely exosomes and microvesicles. Melanocytes and melanoma cell lines have shown that UVA irradiation causes plasma membrane damage that is repaired through lysosomal exocytosis[8,9,10]. Mature melanosomes bind microtubules and undergo bi-directional actin-dependent transport from the perinuclear area towards dendrites[20,21] This transfer is stimulated and regulated through keratinocyte-derived factors[22,23], the delivery mechanism has not been fully characterized. Different mechanisms have been suggested including the heterophagocytosis of melanocyte dendrites by keratinocytes, the release of melanosome-loaded vesicles, the exocytosis of the melanin core with subsequent endocytosis by keratinocytes, transfer by nanotubes or via melanocyte filopodia, and direct fusion with the keratinocyte membrane[24,25,26]. The lysosomal exocytosis was followed by EV shedding from the melanocyte plasma membrane and uptake of EVs by keratinocytes through endocytosis
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