LGR4 Membrane Protein Introduction

Introduction of LGR4

LGR4 is a seven transmembrane G protein-coupled receptor, encoded by LGR4 gene. It belongs to LGRs subgroups B which contain 17 copies of leucine-rich repeats flanked by the N-terminal LRRNT region and the C-terminal LRRCT region. LGR4 is broadly expressed in multiple tissues ranging from the reproductive system, urinary system, sensory organs, digestive system, and the central nervous system, such as kidney, colon, placenta, liver, ovary, testis, thyroid, urinary bladder and brain, indicating LGR4 may be involved in multiple functions in development.

Function of LGR4 Membrane Protein

LGR4 functions via mediating Wnt/β-catenin signaling to involving multiple metabolic activities. LGR4 binds to its ligand, R-spondins, resulting in the activation of the Wnt signaling pathway. And Wnt signaling pathway activation is required in the development of various organs, including liver, kidney, intestine, bone, reproductive tract, eyes and so on. It is reported that LGR4 is a very important mediator for cell regeneration after injury. Moreover, Wnt signaling pathway activation may also play a negative role in innate immunity by inhibiting pattern-recognition and proinflammatory cytokine production. Besides, LGR4 can regulate energy metabolism, including food intake, energy consumption, lipid accumulation, and glucose homeostasis (such as pancreatic β-cell proliferation and insulin secretion). In addition, LGR4, as a positive regulator, may be involved in multiple cancer development and progression by stimulating the proliferation and migration, such as gastric cancer, colorectal cancer, biliary tract cancer, and squamous cell carcinoma. It is also suggested that LGR4 may serve as a therapeutic target for tumor patient.

Fig.1 The G-protein coupled receptors signaling pathway. (Nakata, 2014)

Application of LGR4 Membrane Protein in Literature

1. Da Silva.F., et al. Myocardial-specific R-spondin3 drives proliferation of the coronary stems primarily through the Leucine Rich Repeat G Protein coupled receptor LGR4. Developmental Biology. 2018. PubMed ID: 29859889
   
   

   The study shows that Lgr4-null alleles decrease coronary stem proliferation with the same phenotype seen in R-spondin 3 mutants. These data suggest that LGR4 is the principal R-spondin 3 receptor in the heart.

2. Matsuike R., et al. Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4. Life Sciences. 2018, 201:30-36. PubMed ID: 29572179
   
   

   The research suggests that continuous application of compressive force induces the differentiation of RAW264.7 cells into TRAP-positive multinuclear cells through an increase of RANK and a decrease of LGR4.

3. Yue Z., et al. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells. Faseb Journal. 2018, 32(5):2422-2437. PubMed ID: 29269400
   
   

   The findings identify LGR4, the Wnt signaling component, which plays a crucial role in breast cancer initiation, metastasis, and breast cancer stem cells maintenance.

4. Liu S., et al. R-spondin3-LGR4 signaling protects hepatocytes against DMOG-induced hypoxia/reoxygenation injury through activating β-catenin. Biochem Biophys Res Commun. 2018, 499(1):59-65. PubMed ID: 29555474
   
   

   The study reveals that Rspo3-LGR4 signaling protects hepatocytes from DMOG-induced hypoxia/reoxygenation injury via activating β-catenin.

5. Kang Y.E., et al. Upregulation of RSPO2-GPR48/LGR4 signaling in papillary thyroid carcinoma contributes to tumor progression. Oncotarget. 2017, 8(70):114980-114994. PubMed ID: 29383135
   
   

   The findings suggest that the upregulation of the R-spondin 2-GPR48/LGR4 pathway contributes to tumor aggressiveness in papillary thyroid carcinoma by promoting ERK phosphorylation, suggesting that this pathway represents a novel therapeutic target for treatment of differentiated thyroid cancer.

LGR4 Preparation Options

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Reference

1. Nakata S, et al. (2014). Emerging role for leucine-rich repeat-containing G-protein-coupled receptors LGR5 and LGR4 in cancer stem cells. Cancer Management & Research. 6,171-80.

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