CMKLR1 Membrane Protein Introduction

Introduction of CMKLR1

CMKLR1 is one of the G protein-coupled receptors which have seven transmembrane domains. It is broadly expressed in various human tissues, including spleen, placenta, lung, lymph node, thymus, appendix, bone marrow and so on. The receptor has multifunctional effects, such as regulation of immune response, adipogenesis, angiogenesis, and insulin resistance. So, it is very important for us to investigate CMKLR1 functions, which helps to understand the metabolic activity in organisms.

Function of CMKLR1 Membrane Protein

CMKLR1, also known as chemerin receptor 23 (ChemR23), is a receptor for the chemoattractant adipokine chemerin/RARRES2 and the omega-3 fatty acid derived molecule resolvin E1. The interaction of CMKLR1 and RARRES2 can activate intracellular signaling molecules (SKY, MAPK1/3 (ERK1/2), MAPK14/P38MAPK and PI3K, etc.) leading to multifunctional effects, including decrease of immune responses, strengthening of adipogenesis and angiogenesis. In macrophages, resolvin E1 can regulate the reduced cytokine production by decreasing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. The CMKLR1 gene is widely expressed in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes and endothelial cells. It is suggested that CMKLR1 plays an essential role in the progression of lots of diseases, such as inflammatory disease, adiposity. And the weak expression of CMKLR1 is associated with non-alcoholic steatohepatitis in male individuals. In addition, CMKLR1 may exert a role in peripheral insulin resistance.

Fig.1 Chemerin receptors, CMKLR1, GPR1, and CCRL2 signaling pathways. (Reverchon, 2014)

Application of CMKLR1 Membrane Protein in Literature

1. Li J.J., et al. Chemerin suppresses hepatocellular carcinoma metastasis through CMKLR1-PTEN-Akt axis. Br J Cancer. 2018, 118(10): 1337-1348. PubMed ID: 29717200
   
   

   The research reveals that the expression of chemerin is significantly decreased in hepatocellular carcinoma. And the positive relationship between chemerin and PTEN, as well as the negative correlation between chemerin and p-Akt (Ser473) are also observed in hepatocellular carcinoma clinical samples and intrahepatic mouse model in vivo.

2. Weng C., et al. Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism. American Journal of Translational Research. 2017, 9(6):3096-3104. PubMed ID: 28670396
   
   

   The study shows that no significant difference is observed in serum chemerin levels between obesity-induced hypertension (OIH) group and control group. But chemerin and CMKLR1 expression in aortic arteries and perivascular adipose tissues of the OIH group are higher compared to the control group. Moreover, the OIH group presents an increase of the arterial tension and Rock2 and P-MYPT1 expression.

3. Yang X., et al. Role of chemerin/CMKLR1 in the maintenance of early pregnancy. Front Med. 2018. PubMed ID: 29556954
   
   

   The research is designed to investigate the effect of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. Results show that chemerin/CMKLR1 may be involved in the keeping early pregnancy possibly through mediating ERK1/2 phosphorylation. And blocking chemerin/CMKLR1 signaling may lead to abortion in mouse.

4. Tümmler C., et al. Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo. Oncotarget. 2017, 8(56):95135-95151. PubMed ID: 29221117
   
   

   The article reveals that CMKLR1 antagonist α-NETA decrease the growth and survival of neuroblastoma cells which implicates that chemerin/CMKLR1 axis can act as a promising prognostic factor and possible therapeutic target for neuroblastoma treatment.

5. Huang C., et al. CMKLR1 deficiency influences glucose tolerance and thermogenesis in mice on high fat diet. Biochemical & Biophysical Research Communications. 2016, 473(2):435-441. PubMed ID: 26972253
   
   

   The study reveals that the deficiency of CMKLR1 can enhance glucose intolerance, increase serum insulin levels, and facilitate insulin resistance in mice exposed to high-fat diets. Moreover, the lack of CMKLR1 can influence the thermogenesis process by inhibiting the expression of thermogenesis related genes.

CMKLR1 Preparation Options

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Reference

1. Reverchon M, et al. (2014). Adipokines and the female reproductive tract. International Journal of Endocrinology. 2014(1):232454.

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