title: Disruption of melanosome transport in melanocytes treated with theophylline causes their degradation by autophagy.
abstract: Melanosomes containing melanin are transported from the perinuclear area to the tips of dendrites in epidermal melanocytes, and are then transferred to keratinocytes. Thus, skin color is determined by the amount of melanin synthesized in melanocytes and the subsequent dispersion of melanosomes in the epidermis. Therefore, disrupting intracellular melanosome transport in melanocytes is considered an effective approach to regulate skin color. However, the fate of melanosomes that accumulate in melanocytes due to disrupted intracellular transport is unclear. In this study, we disrupted melanosome transport by knockdown of the motor protein MyosinVa. Knock-down of MyosinVa (M-KD) in cells treated with theophylline significantly down-regulated the mRNA and protein expression levels of tyrosinase. Interestingly, intracellular melanin contents in M-KD cells were decreased. Furthermore, M-KD cells showed activation of autophagy through increased expression of Microtubule-associated protein 1 light chain 3 (LC3) -II and decreased expression of p62. The sum of these results indicate that disruption of melanosome transport causes their degradation by autophagy.
authors.affiliation: Seiwa Kasei Co, Ltd., 1-2-14, Nunoichicho, Higashiosaka, Osaka, 579-8004, Japan. Electronic address: katsuyama_yushi@seiwakasei.co.jp.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Seiwa Kasei Co, Ltd., 1-2-14, Nunoichicho, Higashiosaka, Osaka, 579-8004, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Taira
authors.affiliation: Seiwa Kasei Co, Ltd., 1-2-14, Nunoichicho, Higashiosaka, Osaka, 579-8004, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshioka
authors.affiliation: School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1, Katakuracho, Hachiouji, Tokyo 192-0982, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Okano
authors.affiliation: School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1, Katakuracho, Hachiouji, Tokyo 192-0982, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Masaki
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D020460:Melanosomes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013806:Theophylline / Q000494:pharmacology*
chemical_list: C480860:Map1lc3b protein, mouse; D008543:Melanins; D008869:Microtubule-Associated Proteins; C513082:Myo5a protein, mouse; D034741:RNA, Small Interfering; D013806:Theophylline; D014442:Monophenol Monooxygenase; D024701:Myosin Type V; D018995:Myosin Heavy Chains
keywords: Autophagy; Melanosome transfer; MyosinVa; Tyrosinase