Abstract
Extracellular vesicles (EVs) are heterogeneous membrane-bound complexes of cell-derived and nanosized structures originating from the endosomal system and subsequently released from the plasma membrane. EVs contribute significantly to intercellular communication and are involved in pigmentation processes that rely on tight communication between keratinocytes and melanocytes in the epidermis. Microphthalmia-associated transcription factor (MITF) induces melanogenesis and modulates the expression factors involved in melanosome biogenesis, maturation and dispersal in melanocytes. Here, we evaluated the effects of MITF on the fate of multivesicular bodies and the biogenesis of extracellular vesicles of melanocytes. It was found that MITF increased the expression of subunits of the endosomal sorting complex, required for transport (ESCRT), including VPS37, VPS36B, and tetraspanin CD81, which are key mediators of multivesicular body biogenesis. Over 110 miRNAs, including miR-211-5p, miR-335-5p, let-7g-5p and miR-28a-3p, were differentially expressed in melanocyte-derived EVs after overexpression of MITF in melanocytes. These miRNAs have been reported to be key regulators of plasma protein binding, changes in the cell membrane system and transferase activity. These results suggest that while enhancing melanogenesis, melanocytes may mediate intercellular communication with surrounding cells by serving as EV delivery vehicles.