Cargando…
Identification of novel GPCR partners of the central melanocortin signaling
OBJECTIVE: Homo- or heterodimerization of G protein–coupled receptors (GPCRs) generally alters the normal functioning of these receptors and mediates their responses to a variety of physiological stimuli in vivo. It is well known that melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R)...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458986/ https://www.ncbi.nlm.nih.gov/pubmed/34400348 http://dx.doi.org/10.1016/j.molmet.2021.101317 |
_version_ | 1784571423322275840 |
---|---|
author | Li, Yunpeng Wang, Xiaozhu Lu, Liumei Wang, Meng Zhai, Yue Tai, Xiaolu Dilimulati, Diliqingna Lei, Xiaowei Xu, Jing Zhang, Cong Fu, Yanbin Qu, Shen Li, Qingfeng Zhang, Chao |
author_facet | Li, Yunpeng Wang, Xiaozhu Lu, Liumei Wang, Meng Zhai, Yue Tai, Xiaolu Dilimulati, Diliqingna Lei, Xiaowei Xu, Jing Zhang, Cong Fu, Yanbin Qu, Shen Li, Qingfeng Zhang, Chao |
author_sort | Li, Yunpeng |
collection | PubMed |
description | OBJECTIVE: Homo- or heterodimerization of G protein–coupled receptors (GPCRs) generally alters the normal functioning of these receptors and mediates their responses to a variety of physiological stimuli in vivo. It is well known that melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) are key regulators of appetite and energy homeostasis in the central nervous system (CNS). However, the GPCR partners of MC3R and MC4R are not well understood. Our objective is to analyze single cell RNA-seq datasets of the hypothalamus to explore and identify novel GPCR partners of MC3R and MC4R and examine the pharmacological effect on the downstream signal transduction and membrane translocation of melanocortin receptors. METHODS: We conducted an integrative analysis of multiple single cell RNA-seq datasets to reveal the expression pattern and correlation of GPCR families in the mouse hypothalamus. The emerging GPCRs with important metabolic functions were selected for cloning and co-immunoprecipitation validation. The positive GPCR partners were then tested for the pharmacological activation, competitive binding assay and surface translocation ELISA experiments. RESULTS: Based on the expression pattern of GPCRs and their function enrichment results, we narrowed down the range of potential GPCR interaction with MC3R and MC4R for further confirmation. Co-immunoprecipitation assay verified 23 and 32 novel GPCR partners that interacted with MC3R and MC4R in vitro. The presence of these GPCR partners exhibited different effects in the physiological regulation and signal transduction of MC3R and MC4R. CONCLUSIONS: This work represented the first large-scale screen for the functional GPCR complex of central melanocortin receptors and defined a composite metabolic regulatory GPCR network of the hypothalamic nucleuses. |
format | Online Article Text |
id | pubmed-8458986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84589862021-09-28 Identification of novel GPCR partners of the central melanocortin signaling Li, Yunpeng Wang, Xiaozhu Lu, Liumei Wang, Meng Zhai, Yue Tai, Xiaolu Dilimulati, Diliqingna Lei, Xiaowei Xu, Jing Zhang, Cong Fu, Yanbin Qu, Shen Li, Qingfeng Zhang, Chao Mol Metab Original Article OBJECTIVE: Homo- or heterodimerization of G protein–coupled receptors (GPCRs) generally alters the normal functioning of these receptors and mediates their responses to a variety of physiological stimuli in vivo. It is well known that melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) are key regulators of appetite and energy homeostasis in the central nervous system (CNS). However, the GPCR partners of MC3R and MC4R are not well understood. Our objective is to analyze single cell RNA-seq datasets of the hypothalamus to explore and identify novel GPCR partners of MC3R and MC4R and examine the pharmacological effect on the downstream signal transduction and membrane translocation of melanocortin receptors. METHODS: We conducted an integrative analysis of multiple single cell RNA-seq datasets to reveal the expression pattern and correlation of GPCR families in the mouse hypothalamus. The emerging GPCRs with important metabolic functions were selected for cloning and co-immunoprecipitation validation. The positive GPCR partners were then tested for the pharmacological activation, competitive binding assay and surface translocation ELISA experiments. RESULTS: Based on the expression pattern of GPCRs and their function enrichment results, we narrowed down the range of potential GPCR interaction with MC3R and MC4R for further confirmation. Co-immunoprecipitation assay verified 23 and 32 novel GPCR partners that interacted with MC3R and MC4R in vitro. The presence of these GPCR partners exhibited different effects in the physiological regulation and signal transduction of MC3R and MC4R. CONCLUSIONS: This work represented the first large-scale screen for the functional GPCR complex of central melanocortin receptors and defined a composite metabolic regulatory GPCR network of the hypothalamic nucleuses. Elsevier 2021-08-14 /pmc/articles/PMC8458986/ /pubmed/34400348 http://dx.doi.org/10.1016/j.molmet.2021.101317 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Li, Yunpeng Wang, Xiaozhu Lu, Liumei Wang, Meng Zhai, Yue Tai, Xiaolu Dilimulati, Diliqingna Lei, Xiaowei Xu, Jing Zhang, Cong Fu, Yanbin Qu, Shen Li, Qingfeng Zhang, Chao Identification of novel GPCR partners of the central melanocortin signaling |
title | Identification of novel GPCR partners of the central melanocortin signaling |
title_full | Identification of novel GPCR partners of the central melanocortin signaling |
title_fullStr | Identification of novel GPCR partners of the central melanocortin signaling |
title_full_unstemmed | Identification of novel GPCR partners of the central melanocortin signaling |
title_short | Identification of novel GPCR partners of the central melanocortin signaling |
title_sort | identification of novel gpcr partners of the central melanocortin signaling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458986/ https://www.ncbi.nlm.nih.gov/pubmed/34400348 http://dx.doi.org/10.1016/j.molmet.2021.101317 |
work_keys_str_mv | AT liyunpeng identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT wangxiaozhu identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT luliumei identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT wangmeng identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT zhaiyue identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT taixiaolu identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT dilimulatidiliqingna identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT leixiaowei identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT xujing identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT zhangcong identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT fuyanbin identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT qushen identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT liqingfeng identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling AT zhangchao identificationofnovelgpcrpartnersofthecentralmelanocortinsignaling |