NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis

doi:10.1096/fj.201700564RR

NWIPB OpenIR

	NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis
	Wu, Huali 1,2; Zhao, Yucheng 1; Huang, Qiaoling 1,3,4; Cai, Minxuan 1,3,4; Pan, Qi 1,3,4; Fu, Mengsi 1,3,4; An, Xiaohong 1,3,4; Xia, Zhenjiang 5; Liu, Meng 6; Jin, Yu 7; He, Ling 2; Shang, Jing 1,3,4,5
	2018-06-01
发表期刊	FASEB JOURNAL
ISSN	0892-6638
卷号	32 期号:6 页码:3193-3214
文章类型	Article
摘要	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.
关键词	Protein-protein Interaction Signaling Cascades Nk1r 5-ht1ar Heterdimerization
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.1096/fj.201700564RR
关键词[WOS]	RESONANCE ENERGY-TRANSFER ; CELL-SURFACE EXPRESSION ; SUBSTANCE-P ; SEROTONIN RECEPTORS ; NEUROKININ-1 RECEPTOR ; MELANIN SYNTHESIS ; TRYPTOPHAN-HYDROXYLASE ; ENDOPLASMIC-RETICULUM ; TRANSCRIPTION FACTOR ; SKIN PIGMENTATION
收录类别	SCI
语种	英语
项目资助者	Science and Technology Plan Projects in Qinghai Province(2015-ZJ-733) ; Science and Technology Plan Projects in Xinjiang(2014AB043) ; National Natural Science Foundation of China(81603216) ; CMA-L'OREAL China Skin/Hair Grant(S2017140917) ; One Hundred Person Project of the Chinese Academy of Sciences, Applied Basic Research Programs of Qinghai Province(Y229461211) ; Prospective Joint Research Project of Jiangsu Province(BY2016078-02)
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biology ; Cell Biology
WOS记录号	WOS:000432546000025
出版者	FEDERATION AMER SOC EXP BIOL
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/13805
专题	中国科学院西北高原生物研究所
通讯作者	Shang, Jing
作者单位	1.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China 2.China Pharmaceut Univ, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China 3.China Pharmaceut Univ, Jiangsu Key Lab Tradit Chinese Med TCM Evaluat &, Nanjing, Jiangsu, Peoples R China 4.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing, Jiangsu, Peoples R China 5.Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Key Lab Tibetan Med Pharmacol & Safety Ev, Xining, Qinghai, Peoples R China 6.Xinjiang Med Univ, Affiliated Tumor Hosp, Urumqi, Peoples R China 7.Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA
推荐引用方式 GB/T 7714	Wu, Huali,Zhao, Yucheng,Huang, Qiaoling,et al. NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis[J]. FASEB JOURNAL,2018,32(6):3193-3214.
APA	Wu, Huali.,Zhao, Yucheng.,Huang, Qiaoling.,Cai, Minxuan.,Pan, Qi.,...&Shang, Jing.(2018).NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis.FASEB JOURNAL,32(6),3193-3214.
MLA	Wu, Huali,et al."NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis".FASEB JOURNAL 32.6(2018):3193-3214.