ReferenceID 2768
Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin
J Dermatol Sci
Background: Melanosomes are intracellularly transported from the perinuclear region to the cell periphery and then to neighboring keratinocytes. We recently reported that the flavonoid rhamnazin suppresses melanosomal tr
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- Reference Id
- 2768
- Evidence Id
- 19358
- Core Evidence Id
- 19358
- Source Reference Id
- 5535
- Herb2 Reference Id
- HBREF006332
- Subject Paper Key
- HBIN042151_34955374
- Pubmed Id
- 34955374
- Doi
- 10.1016/j.jdermsci.2021.12.003
- Paper Title
- Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin
- Paper Abstract
- Background: Melanosomes are intracellularly transported from the perinuclear region to the cell periphery and then to neighboring keratinocytes. We recently reported that the flavonoid rhamnazin suppresses melanosomal transport within pigment cells, yet the action mechanism remained unclear. Objective: Our aim was to elucidate how rhamnazin influences the intracellular transport of melanosomes. Methods: A melanosome distribution assay and immunostaining were performed using B16F10 mouse melanoma cells and normal human epidermal melanocytes, respectively. Expression levels of melanosome transport-related proteins, including melanophilin (MLPH), RAB27A, and myosin VA (MYO5A), were analyzed by immunoblotting. Ubiquitinated MLPH was detected using a commercial ubiquitin detection kit. To investigate the interaction between rhamnazin and MLPH, we prepared rhamnazin conjugated with magnetic FG beads. Results: Immunoblotting analysis revealed that rhamnazin specifically reduces the expression of MLPH but not RAB27A or MYO5A proteins. The ubiquitin detection assay, which made use of a proteasome inhibitor, showed that MLPH accumulated as a polyubiquitinated protein after treatment with rhamnazin. We speculated that the affinity of rhamnazin for the components of the melanosome transport-related tripartite complex may alter the stability of the formation of the tripartite assembly. By using affinity-based techniques with B16F10 whole cell lysates or recombinant MLPH and RAB27A proteins, we revealed the interaction of rhamnazin with the components of the tripartite complex. Conclusion: We found that rhamnazin inhibits intracellular transport of melanosomes through proteasomal degradation of MLPH. Our results suggest that topical application of rhamnazin may provide a new approach for treating skin pigmentation disorders.
- Journal
- J Dermatol Sci
- Publish Year
- 2021
- Experiment Subject
- mouse; human; b16f10 mouse melanoma cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Melanoma; Skin Pigmentation Disorders
- Paper Title Cn
- Paper Title En
- Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin
- Bilingual Status
- semi_complete