CNR2 Membrane Protein Introduction

Introduction of CNR2

CNR2, also known as CB2, belongs to a G protein-coupled receptor from the cannabinoid receptor family, encoded by the CNR2 gene. It has seven transmembrane spanning domains, a glycosylated N-terminal and an intracellular C-terminal. Approximately 44% amino acid similarity is found in the human CNR1 and CNR2 receptors. And CNR2 receptor possesses about 360 amino acids, with a shorter than the 473-amino-acid-long CNR1 receptor.

Function of CNR2 Membrane Protein

Like the CNR1 receptors, activated CNR2 receptors by binding to cannabinoid inhibit the activity of adenylyl cyclase leading to a decrease of intracellular second messenger cAMP concentration. CNR2 receptors are involved in the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which plays a critical role in regulating a number of important cellular processes in both mature and developing tissues, such as cell migration, neuroplasticity, and long-term memory formation. Moreover, CNR2 also exerts a role in immune response. The CB2 variants are associated with liver necroinflammation in chronic hepatitis patients with HIV/HCV coinfection. CB2-63 RR variant in the immune-mediated disorders (IMD) group is significantly higher than in non-IMD group. Besides, CNR2 may be involved in the pathological process of neurodegenerative disorders. Some studies showed that CB2 in dopamine neurons could suppress psychomotor behaviors, anxiety, depression, and pain sensation. Hence, it is also suggested that CB2 may act as a possible therapeutic target in the treatment of neurodegenerative disorders, such as Alzheimer's disease.

Fig.1 Activation of CB2 receptors affects different signaling pathways. (Dhopeshwarkar, 2014)

Application of CNR2 Membrane Protein in Literature

1. López A., et al. Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer’s disease. Journal of Neuroinflammation. 2018, 15(1): 158. PubMed ID: 29793509
   
   

   The study shows that CB2 receptors are up-regulated in central nervous system on the condition of amyloid-triggered neuroinflammation. And CB2R null in Alzheimer's disease mice presents decreased neuritic plaques with no changes in IL1β expression which also suggests that CB2R plays a complex role in the response to plaque formation.

2. .Wang J., et al. Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression. Journal of Cancer Research & Clinical Oncology. 2018, 144(1): 1-14. PubMed ID: 28993942
   
   

   The study finds that CB2 is up-regulated in renal cell carcinoma (RCC) and can be regarded as an independent prognostic factor for over survival of RCC. Test in vitro suggests that the expression of CB2 significantly decreases cell proliferation and migration, and induces cell cycle arrest in G2/M of RCC cells.

3. Tahamtan A., et al. Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice. Virulence. 2017, 9(1): 217-230. PubMed ID: 28992427
   
   

   The finding shows that CB2 is associated with the severity of respiratory syncytial virus (RSV) infection. And this also suggests that CB2 may be used as a therapeutic target in RSV infection.

4. Rowley S., et al. Cannabinoid receptor 1/2 double-knockout mice develop epilepsy. Epilepsia. 2017, 58(12): e162-e166. PubMed ID: 29105060
   
   

   The research shows that the CB1 and CB2 double-knockout mice can present an exacerbated neurological phenotype. 30% of double-knockout mice exhibited provoked behavioral seizures, and 80% were found to be epileptic following 24/7 video-electroencephalographic monitoring.

5. Meletta R., et al. Cannabinoid receptor type 2 (CB2) as one of the candidate genes in human carotid plaque imaging: Evaluation of the novel radiotracer [¹¹C]RS-016 targeting CB2 in atherosclerosis. Nuclear Medicine & Biology. 2017, 47: 31-43. PubMed ID: 28104528
   
   

   The study finds that 28 human genes unconventionally expressed in atherosclerotic plaques compared to normal arteries. CB2 is one of the abnormal genes and upregulated in human atherosclerotic plaques. Hence, CB2 may serve as novel imaging or therapeutic targets.

CNR2 Preparation Options

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Reference

1. Dhopeshwarkar A and Mackie K. (2014). CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Molecular Pharmacology. 86(4), 430-7.

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