title: Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity.
abstract: The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated. Here, we discuss the role of MATP in melanin production. The SLC45A2 gene is highly enriched in human melanocytes and melanoma cell lines, and its protein, MATP, is located in melanosomes. The knockdown of MATP using siRNAs reduced melanin content and tyrosinase activity without any morphological change in melanosomes or the expression of melanogenesis-related proteins. Interestingly, the knockdown of MATP significantly lowered the melanosomal pH, as verified through DAMP analysis, suggesting that MATP regulates melanosomal pH and therefore affects tyrosinase activity. Finally, we found that the reduction of tyrosinase activity associated with the knockdown of MATP was readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. Considering that copper is an important element for tyrosinase activity and that its binding to tyrosinase depends on melanosomal pH, MATP may play an important role in regulating tyrosinase activity via controlling melanosomal pH.
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Bum-Ho
authors.initials: BH
authors.lastname: Bin
authors.affiliation: Department of Chemical Engineering, POSTECH, Pohang, Republic of Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Bhin
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Misun
authors.initials: M
authors.lastname: Shin
authors.affiliation: Gyeonggi Bio Center, Gyeonggi Institute of Science & Technology Promotion, Suwon, Republic of Korea.
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Nam
authors.affiliation: Gyeonggi Bio Center, Gyeonggi Institute of Science & Technology Promotion, Suwon, Republic of Korea.
authors.forename: Dong-Hwa
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors.forename: Ai-Young
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering, POSTECH, Pohang, Republic of Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Cho
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction
chemical_list: D000951:Antigens, Neoplasm; D007211:Indoles; D008543:Melanins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human; C009904:melanogen; D014442:Monophenol Monooxygenase