LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation
Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPR48), a member of the GPCR (G protein-coupled receptors) superfamily, subfamily B, is a common intestinal crypt stem cell marker. It binds R-spondins/Norrin as classical ligands and plays a crucial role in Wnt signaling potentiation...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.867001/full |
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| author | Joanna Filipowska Nagesha G. Kondegowda Nancy Leon-Rivera Sangeeta Dhawan Rupangi C. Vasavada |
| author_facet | Joanna Filipowska Nagesha G. Kondegowda Nancy Leon-Rivera Sangeeta Dhawan Rupangi C. Vasavada |
| author_sort | Joanna Filipowska |
| collection | DOAJ |
| description | Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPR48), a member of the GPCR (G protein-coupled receptors) superfamily, subfamily B, is a common intestinal crypt stem cell marker. It binds R-spondins/Norrin as classical ligands and plays a crucial role in Wnt signaling potentiation. Interaction between LGR4 and R-spondins initiates many Wnt-driven developmental processes, e.g., kidney, eye, or reproductive tract formation, as well as intestinal crypt (Paneth) stem cell pool maintenance. Besides the well-described role of LGR4 in development, several novel functions of this receptor have recently been discovered. In this context, LGR4 was indicated to participate in TGFβ and NFκB signaling regulation in hematopoietic precursors and intestinal cells, respectively, and found to be a new, alternative receptor for RANKL (Receptor Activator of NF kappa B Ligand) in bone cells. LGR4 inhibits the process of osteoclast differentiation, by antagonizing the interaction between RANK (Receptor Activator of NF kappa B) and its ligand-RANKL. It is also known to trigger anti-inflammatory responses in different tissues (liver, intestine, cardiac cells, and skin), serve as a sensor of the circadian clock in the liver, regulate adipogenesis and energy expenditure in adipose tissue and skeletal muscles, respectively. The extracellular domain of LGR4 (LGR4-ECD) has emerged as a potential new therapeutic for osteoporosis and cancer. LGR4 integrates different signaling pathways and regulates various cellular processes vital for maintaining whole-body homeostasis. Yet, the role of LGR4 in many cell types (e.g. pancreatic beta cells) and diseases (e.g., diabetes) remains to be elucidated. Considering the broad spectrum of LGR4 actions, this review aims to discuss both canonical and novel roles of LGR4, with emphasis on emerging research directions focused on this receptor. |
| first_indexed | 2024-04-14T00:28:42Z |
| format | Article |
| id | doaj.art-be94f9f3296b45a694f8968b47c9bfc6 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-14T00:28:42Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-be94f9f3296b45a694f8968b47c9bfc62022-12-22T02:22:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-05-011310.3389/fendo.2022.867001867001LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic RegulationJoanna FilipowskaNagesha G. KondegowdaNancy Leon-RiveraSangeeta DhawanRupangi C. VasavadaLeucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPR48), a member of the GPCR (G protein-coupled receptors) superfamily, subfamily B, is a common intestinal crypt stem cell marker. It binds R-spondins/Norrin as classical ligands and plays a crucial role in Wnt signaling potentiation. Interaction between LGR4 and R-spondins initiates many Wnt-driven developmental processes, e.g., kidney, eye, or reproductive tract formation, as well as intestinal crypt (Paneth) stem cell pool maintenance. Besides the well-described role of LGR4 in development, several novel functions of this receptor have recently been discovered. In this context, LGR4 was indicated to participate in TGFβ and NFκB signaling regulation in hematopoietic precursors and intestinal cells, respectively, and found to be a new, alternative receptor for RANKL (Receptor Activator of NF kappa B Ligand) in bone cells. LGR4 inhibits the process of osteoclast differentiation, by antagonizing the interaction between RANK (Receptor Activator of NF kappa B) and its ligand-RANKL. It is also known to trigger anti-inflammatory responses in different tissues (liver, intestine, cardiac cells, and skin), serve as a sensor of the circadian clock in the liver, regulate adipogenesis and energy expenditure in adipose tissue and skeletal muscles, respectively. The extracellular domain of LGR4 (LGR4-ECD) has emerged as a potential new therapeutic for osteoporosis and cancer. LGR4 integrates different signaling pathways and regulates various cellular processes vital for maintaining whole-body homeostasis. Yet, the role of LGR4 in many cell types (e.g. pancreatic beta cells) and diseases (e.g., diabetes) remains to be elucidated. Considering the broad spectrum of LGR4 actions, this review aims to discuss both canonical and novel roles of LGR4, with emphasis on emerging research directions focused on this receptor.https://www.frontiersin.org/articles/10.3389/fendo.2022.867001/fullLGR4GPCRs (G protein-coupled receptors)Wnt signalingRANKL (Receptor Activator for Nuclear Factor k B Ligand)inflammationNFκB - Nuclear Factor κB |
| spellingShingle | Joanna Filipowska Nagesha G. Kondegowda Nancy Leon-Rivera Sangeeta Dhawan Rupangi C. Vasavada LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation Frontiers in Endocrinology LGR4 GPCRs (G protein-coupled receptors) Wnt signaling RANKL (Receptor Activator for Nuclear Factor k B Ligand) inflammation NFκB - Nuclear Factor κB |
| title | LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation |
| title_full | LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation |
| title_fullStr | LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation |
| title_full_unstemmed | LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation |
| title_short | LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation |
| title_sort | lgr4 a g protein coupled receptor with a systemic role from development to metabolic regulation |
| topic | LGR4 GPCRs (G protein-coupled receptors) Wnt signaling RANKL (Receptor Activator for Nuclear Factor k B Ligand) inflammation NFκB - Nuclear Factor κB |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.867001/full |
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