LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.
GPCRs (G protein-coupled receptors)
LGR4
LGR4-ECD
NFκB - Nuclear Factor κB
RANKL (Receptor Activator for Nuclear Factor k B Ligand)
Wnt signaling
inflammation
miRNA34 a/c
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2022
2022
Historique:
received:
31
01
2022
accepted:
21
04
2022
entrez:
16
6
2022
pubmed:
17
6
2022
medline:
18
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35707461
doi: 10.3389/fendo.2022.867001
pmc: PMC9190282
doi:
Substances chimiques
Ligands
0
NF-kappa B
0
Receptor Activator of Nuclear Factor-kappa B
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
867001Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK120523
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125856
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102893
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120523
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK104162
Pays : United States
Informations de copyright
Copyright © 2022 Filipowska, Kondegowda, Leon-Rivera, Dhawan and Vasavada.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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