title: Microtubule-associated protein light chain 3 is involved in melanogenesis via regulation of MITF expression in melanocytes.
abstract: Although autophagy plays a role in melanogenesis by regulating melanosome degradation and biogenesis in melanocytes, a detailed understanding of the regulatory functions of autophagy factors is lacking. Here, we report a mechanistic link between microtubule-associated protein light chain 3 (LC3) activation and melanogenesis. We observed high expression of LC3 in melanosome-associated pigment-rich melanocytic nevi of sun-exposed skin, as indicated by patterns of melanosomal protein MART1 expression. Rapamycin-induced autophagy significantly increased the melanin index, tyrosinase activity and expression of several proteins linked to melanosome biogenesis, including microphthalmia transcription factor (MITF), pre-melanosome protein and tyrosinase, in Melan-a melanocytes. siRNA-mediated knockdown of LC3, but not beclin-1 or ATG5, decreased melanin content and tyrosinase activity. LC3 knockdown also markedly inhibited MITF expression and subsequent rapamycin-induced melanosome formation. More importantly, LC3 knockdown suppressed α-MSH-mediated melanogenesis by attenuating cAMP response element-binding protein (CREB) phosphorylation and MITF expression in Melan-a cells via decreased extracellular signal-regulated kinase (ERK) activity. Overexpression of constitutively active ERK reversed the effect of LC3 knockdown on CREB phosphorylation and MITF expression. These findings demonstrate that LC3 contributes to melanogenesis by increasing ERK-dependent MITF expression, thereby providing a mechanistic insight into the signaling network that links autophagy to melanogenesis.
authors.affiliation: Department of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Yun
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Jo
authors.affiliation: Department of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Bang
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
authors.affiliation: Department of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Chang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C480860:Map1lc3b protein, mouse; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D008869:Microtubule-Associated Proteins; D000521:alpha-MSH; D048049:Extracellular Signal-Regulated MAP Kinases
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