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Formation of Kiss1R/GPER Heterocomplexes Negatively Regulates Kiss1R-mediated Signalling through Limiting Receptor Cell Surface Expression
Ke,Ran1; Lok,Samson Ian Sam1; Singh,Kailash2; Chow,Billy Kwok Chong2; Janovjak,Harald3; Lee,Leo Tsz On1,4
2021-04-02
Source PublicationJournal of Molecular Biology
ISSN0022-2836
Volume433Issue:7
Abstract

Kisspeptin receptor (Kiss1R) is an important receptor that plays central regulatory roles in reproduction by regulating hormone release in the hypothalamus. We hypothesize that the formation of heterocomplexes between Kiss1R and other hypothalamus G protein-coupled receptors (GPCRs) affects their cellular signaling. Through screening of potential interactions between Kiss1R and hypothalamus GPCRs, we identified G protein-coupled estrogen receptor (GPER) as one interaction partner of Kiss1R. Based on the recognised function of kisspeptin and estrogen in regulating the reproductive system, we investigated the Kiss1R/GPER heterocomplex in more detail and revealed that complex formation significantly reduced Kiss1R-mediated signaling. GPER did not directly antagonize Kiss1R conformational changes upon ligand binding, but it rather reduced the cell surface expression of Kiss1R. These results therefore demonstrate a regulatory mechanism of hypothalamic hormone receptors via receptor cooperation in the reproductive system and modulation of receptor sensitivity.

KeywordCell Signaling g Protein-coupled Estrogen Receptor Gpcr Dimerization Kisspeptin Receptor
DOI10.1016/j.jmb.2021.166843
URLView the original
Language英語English
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Document TypeJournal article
CollectionFaculty of Health Sciences
Centre of Reproduction, Development and Aging
Corresponding AuthorLee,Leo Tsz On
Affiliation1.Centre of Reproduction,Development and Aging,Faculty of Health Sciences,University of Macau,Taipa,Macao
2.School of Biological Sciences,The University of Hong Kong,Pokfulam Road,Hong Kong
3.EMBL Australia,Australian Regenerative Medicine Institute (ARMI),Faculty of Medicine,Nursing and Health Sciences,Monash University,Clayton/Melbourne,Australia
4.Cancer Centre,Faculty of Health Sciences,University of Macau,Taipa,Macao
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences;  Cancer Centre
Recommended Citation
GB/T 7714
Ke,Ran,Lok,Samson Ian Sam,Singh,Kailash,et al. Formation of Kiss1R/GPER Heterocomplexes Negatively Regulates Kiss1R-mediated Signalling through Limiting Receptor Cell Surface Expression[J]. Journal of Molecular Biology,2021,433(7).
APA Ke,Ran,Lok,Samson Ian Sam,Singh,Kailash,Chow,Billy Kwok Chong,Janovjak,Harald,&Lee,Leo Tsz On.(2021).Formation of Kiss1R/GPER Heterocomplexes Negatively Regulates Kiss1R-mediated Signalling through Limiting Receptor Cell Surface Expression.Journal of Molecular Biology,433(7).
MLA Ke,Ran,et al."Formation of Kiss1R/GPER Heterocomplexes Negatively Regulates Kiss1R-mediated Signalling through Limiting Receptor Cell Surface Expression".Journal of Molecular Biology 433.7(2021).
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