PUBLICATION
NK1R/5-HT1AR interaction is related to the regulation of melanogenesis
- Authors
- Wu, H., Zhao, Y., Huang, Q., Cai, M., Pan, Q., Fu, M., An, X., Xia, Z., Liu, M., Jin, Y., He, L., Shang, J.
- ID
- ZDB-PUB-180214-5
- Date
- 2018
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32(6): 3193-3214 (Journal)
- Registered Authors
- Shang, Jing
- Keywords
- 5-HT1AR, NK1R, heterdimerization, protein—protein interaction, signaling cascades
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- HEK293 Cells
- Humans
- Melanins/biosynthesis*
- Melanins/genetics
- Mice
- Neurokinin-1 Receptor Antagonists/pharmacology
- Piperazines/pharmacology
- Pyridines/pharmacology
- Receptor, Serotonin, 5-HT1A/genetics
- Receptor, Serotonin, 5-HT1A/metabolism*
- Receptors, Neurokinin-1/genetics
- Receptors, Neurokinin-1/metabolism*
- Serotonin 5-HT1 Receptor Antagonists/pharmacology
- Skin/metabolism*
- Skin/pathology
- Skin Pigmentation*
- Stress, Psychological/genetics
- Stress, Psychological/metabolism
- Substance P/metabolism
- Substance P/pharmacology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 29430989 Full text @ FASEB J.
Citation
Wu, H., Zhao, Y., Huang, Q., Cai, M., Pan, Q., Fu, M., An, X., Xia, Z., Liu, M., Jin, Y., He, L., Shang, J. (2018) NK1R/5-HT1AR interaction is related to the regulation of melanogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 32(6):3193-3214.
Abstract
Substance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR. The present study aimed at assessing the possible existence of NK1R-5-HTR interactions and related melanogenic functions. Western blot and PCR detection revealed that SP reduced expression of 5-HT1A receptor via the NK1 receptor. Biochemical analyses showed that NK1R and 5-HT1AR could colocalize and interact in a cell and in the skin. When the N terminus of the NK1R protein was removed NK1R surface targeting was prevented, the interaction between NK1R-5-HT1AR decreased, and the depigmentation caused by SP and WAY100635 could be rescued. Importantly, pharmaceutical coadministration of NK1R agonist (SP) and 5-HT1A antagonist (WAY100635) enhanced the NK1-5-HT1A receptor coimmunoprecipitation along with the depigmentary response. SP and WAY100635 cooperation elicited activation of a signaling cascade (the extracellular, regulated protein kinase p-JNK signaling pathway) and inhibition of p70S6K1 phosphorylation and greatly reduced melanin production in vitro and in vivo in mice and zebrafish. Moreover, the SP-induced depigmentation response did not be occur in 5-htr1aa+/- zebrafish embryos. Taken together, the results of our systemic study increases our knowledge of the roles of NK1R and 5-HT1AR in melanogenesis and provides possible, novel therapeutic strategies for treatment of skin hypo/hyperpigmentation.-Wu, H., Zhao, Y., Huang, Q., Cai, M., Pan, Q., Fu, M., An, X., Xia, Z., Liu, M., Jin, Y., He, L., Shang, J. NK1R/5-HT1AR interaction is related to the regulation of melanogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping