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The melanocortin-1 receptor reversely regulates the melanin synthesis and migration of melanoma cells via dimerization-induced conformational changes
- Title
- The melanocortin-1 receptor reversely regulates the melanin synthesis and migration of melanoma cells via dimerization-induced conformational changes
- Authors
- Park, Jisu; Jeong, Dayun; Jang, Bohee; Oh, Eok-Soo
- Ewha Authors
- 오억수; 장보희
- SCOPUS Author ID
- 오억수; 장보희
- Issue Date
- 2019
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- ISSN
- 0006-291X
1090-2104
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS vol. 518, no. 4, pp. 739 - 745
- Keywords
- Melanocortin-1 receptor; Syndecan-2; Migration; Melanin synthesis; Dimerization
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- We previously reported that the melanocortin-1 receptor (MC1R), a key regulator of melanogenesis, regulates cell migration; however, the detailed mechanism remained unknown. Since the homodimerization of MC1R by four inter-subunit disulfide bonds is known to be functionally important for melanogenesis, we investigated the importance of MC1R dimerization for cell migration. Unlike the wild-type MC1R, the dimerization-defective mutant MC1R in which four critical Cys residues were replaced with Ala residues (Cys35-267-273-275Ala) significantly inhibited melanin synthesis but enhanced cell migration in human MNT-1 and A375 melanoma cells. This suggests that there may be a reverse correlation between melanin synthesis and cell migration. Interestingly, melanoma cells expressing the dimerization-defective mutant exhibited enhanced expression of the cell surface heparan sulfate proteoglycan, syndecan-2, and knockdown of syndecan-2 expression decreased the mutant-mediated cell migration. Consistently, ASIP, an antagonist of MC1R, enhanced syndecan-2 expression and cell migration and reversed the alpha-melanocyte-stimulating hormone (alpha-MSH)-mediated inhibition of syndecan-2 expression. Furthermore, alpha-MSH reduced the cell migration of MNT1 cells expressing wild-type MC1R but not its dimerization-defective mutant. Together, these data strongly suggest that MC1R reversely regulates melanin synthesis and migration via the conformational changes induced by dimerization. (C) 2019 Elsevier Inc. All rights reserved.
- DOI
- 10.1016/j.bbrc.2019.08.123
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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