|
|||||
|
|
Formation of Kiss1R/GPER Heterocomplexes Negatively Regulates Kiss1R-mediated Signalling through Limiting Receptor Cell Surface Expression |
|
| Institution: | 1. Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau;2. School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region;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, Macau;1. Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA;2. Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA;3. Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA;4. The Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA;5. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA;1. Max Planck Institute for Medical Research, Department of Biomolecular Mechanismsm Heidelberg, Germany;2. Karlsruhe Institute of Technology, Steinbuch Centre for Computing and Department of Physics, Eggenstein-Leopoldshafen, Germany;3. Institute of Biochemistry, Graz University of Technology. Graz, Austria;4. Institute for Advanced Simulation, Jülich Supercomputing Center, Jülich, Germany;1. Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;2. Department of Life Sciences, Korea University, Seoul, Republic of Korea;3. Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA;1. UMR INRAE 0085, CNRS 7247, Physiologie de la Reproduction et des Comportements, Centre INRA Val de Loire, 37380 Nouzilly, France;2. UMR MEPHI D-258, I, IRD, Aix Marseille Université, 19-21 Boulevard Jean Moulin, 13005 Marseille, France;3. CNRS SNC 5039, 13005 Marseille, France;4. EA GICC 7501, CHRU de Tours, 37044 TOURS Cedex 09, France;5. Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA;6. Weill Cornell Medical College, Cornell University, New York, NY, USA;7. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA |
| 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. |
| Keywords: | GPCR dimerization Kisspeptin receptor G protein-coupled estrogen receptor cell signaling BRET"} {"#name":"keyword" "$":{"id":"k0030"} "$$":[{"#name":"text" "_":"Bioluminescence resonance energy transfer FRET"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"Fluorescence resonance energy transfer GnIH"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"Gonadotropin-inhibitory hormone GnRH"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"Gonadotropin-releasing hormone GPCRs"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"G protein-coupled receptors GPER"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"G protein-coupled estrogen receptor ICL"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"Intracellular loop Kiss1R"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"Kisspeptin receptor NPFFR1"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"Neuropeptide FF receptor 1 PAC1R"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 1 TM"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"Transmembrane |
| 本文献已被 ScienceDirect 等数据库收录！ | |