title: Role of Ser129 phosphorylation of α-synuclein in melanoma cells.
abstract: α-Synuclein, a protein central to Parkinson's disease, is frequently expressed in melanoma tissues, but not in non-melanocytic cutaneous carcinoma and normal skin. Thus, α-synuclein is not only related to Parkinson's disease, but also to melanoma. Recently, epidemiologists reported co-occurrence of melanoma and Parkinson's disease in patients, suggesting that these diseases could share common pathogenetic components and that α-synuclein might be one of these. In Parkinson's disease, phosphorylation of α-synuclein at Ser129 plays an important role in the pathobiology. However, its role in melanoma is not known. Here, we show the biological relevance of Ser129 phosphorylation in human melanoma cells. First, we have identified an antibody that reacts with Ser129-unphosphorylated α-synuclein but not with Ser129-phosphorylated α-synuclein. Using this and other antibodies to α-synuclein, we investigated the role of Ser129 phosphorylation in human melanoma SK-MEL28 and SK-MEL5 cells. Our immunofluorescence microscopy showed that the Ser129-phosphorylated form, but not the Ser129-unphosphorylated form, of α-synuclein localizes to dot-like structures at the cell surface and the extracellular space. Furthermore, immuno-electron microscopy showed that the melanoma cells release microvesicles in which Ser129-phosphorylated α-synuclein localizes to the vesicular membrane. Taken together, our studies suggest that the phosphorylation of Ser129 leads to the cell surface translocation of α-synuclein along the microtubule network and its subsequent vesicular release in melanoma cells.
authors.affiliation: Department of Medicine, GRU Cancer Center, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Byung Rho
authors.initials: BR
authors.lastname: Lee
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Anil G
authors.initials: AG
authors.lastname: Cashikar
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D051844:alpha-Synuclein; D012694:Serine