CRHR1 Membrane Protein Introduction

Introduction of CRHR1

CRHR1, encoded by CRHR1 gene, also known as CRF1, is a cell-surface protein. It belongs to G-protein coupled receptor family which has seven transmembrane domains. CRHR1 is located at 17q12-q22. The molecular weight of CRHR1 is 50,719 in human. The extracellular domain of receptor responds to peptide hormones, corticotropin-releasing hormone (CRH) and urocortin (UCN), involved in the regulation of response to stress. Most studies have been designed to investigate the CRHR1 possible role in regulation response to stress and in potential drug targets for depression and anxiety.

Function of CRHR1 Membrane Protein

CRHR1 is essentially a G-protein coupled receptor for corticotropin-releasing factor and UCN (urocortin). CRHR1 is widely distributed throughout the brain. CRHR1 binds to its ligands, neuropeptides of the corticotropin-releasing hormone family which are a major regulator of the hypothalamic-pituitary-adrenal pathway (HPA). Moreover, HPA is an important part of the neuroendocrine system, involved in controlling the reaction of stress and regulating many physical activities, such as the digestive system, immune system, mood and emotions, sexuality, as well as the energy storage and consumption. Besides, the binding of CRH and CRHR1 can also promote the activation of the receptors, and activate adenylyl cyclase signaling pathway, resulting in an increase of intracellular second messenger cAMP levels. The signal can be transmitted along multiple signal transduction cascades, such as PKC and MAPK. Most studies have indicated that the CRHR1 is very essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response, and obesity. Mice lacking the CRHR1 impaire stress response and display a reduced anxiety-like and cognitive performance. These also suggest that CRHR1 can be considered as a drug target for depression and anxiety.

Fig.1 CRH-CRHR1 system. (Bonfiglio, 2011).

Application of CRHR1 Membrane Protein in Literature

1. 1.Roy A., et al. Family environment interacts with CRHR1 rs17689918 to predict mental health and behavioral outcomes. Progress in neuro-psychopharmacology & biological psychiatry. 2018, 86: 45-51. PubMed ID: 29772307
   
   

   The study assesses the effect of SNP rs17689918 in CRHR1 interaction with the environment on behavioral and mental health. Results indicate that male A-allele carriers and female GG homozygotes can present low familial warmth with aggression, higher number of stressful life events with aggression, and stressful life events with anxious-depressive symptoms.

2. Schartner C., et al. CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder? European Neuropsychopharmacology the Journal of the European College of Neuropsychopharmacology. 2017, 27(4): 360-371. PubMed ID: 28233670
   
   

   The study implicates that CRHR1 methylation is significantly decreased in panic disorder patients and in healthy person with high Beck Anxiety Inventory (BAI) scores. Moreover, CRHR1 hypomethylation can upregulate the CRHR1 gene expression. These suggest the upregulated CRHR1 gene expression regulated by hypomethylation may be associated with stress response and panic disorder risk.

3. Chen H., et al. Activation of corticotropin-releasing factor receptor 1 aggravates dextran sodium sulphate-induced colitis in mice by promoting M1 macrophage polarization. Molecular Medicine Reports. 2018, 17(1): 234-242. PubMed ID: 29115460
   
   

   The research aims to investigate the role of CRF-R1 in the development of mucosal inflammation induced by dextran sulphate sodium (DSS). Results show that the CRF-R1 levels are associated with the severity of DSS-induced colitis. These also suggest that CRF-R1 may act as a pro-inflammatory role in the DSS-induced colitis.

4. Alderman S L., et al. Corticotropin-releasing factor regulates caspase-3 and may protect developing zebrafish from stress-induced apoptosis. General and Comparative Endocrinology. 2018, 265: 207-213. PubMed ID: 29807032
   
   

   This study identifies the corticotropin-releasing factor (CRF) role in the regulation of stress-induced apoptosis in a vertebrate model species. CRF regulates caspase-3 activity through a CRF-R1-dependent pathway and protects zebrafish from stress-induced apoptosis.

5. Grimm S., et al. The Interaction of Corticotropin-Releasing Hormone Receptor Gene and Early Life Stress on Emotional Empathy. Behavioural Brain Research. 2017, 329: 180-185. PubMed ID: 28461011
   
   

   The research reveals that CRHR1 polymorphisms are associated with the regulation of the effect of early life stress (ELS) on emotional empathy. And adults with a vulnerable genotype may impair emotional empathy when they are exposed to ELS.

6. Ludwig B., et al. Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach. Frontiers in Psychiatry. 2018, 9: 165. PubMed ID: 29755375
   
   

   This article reports that the impact of childhood trauma and CRHR1 polymorphisms on previous suicide attempts could be reflected by the single nucleotide polymorphisms (SNPs) rs7209436 and rs110402.

7. Xu Y.J., et al. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations. Faseb Journal. 2018: fj201700948RR. PubMed ID: 29543532
   
   

   This article suggests that CRH and CRHR1 gene expression can be programed by prenatal synthetic glucocorticoids exposure in hippocampus across 2 generations, leading to depression-like behavior. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.

8. Savarese A. and Lasek A. W. Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3. Psychoneuroendocrinology. 2018, 92: 13-20. PubMed ID: 29609111
   
   

   This article shows that altering CRHR1 expression maybe make Lmo3 promote anxiety-like behavior specifically in the BLA,. This study supports a role for Lmo3 in anxiety-like behavior for the first time.

9. Zhao Y, et al. CRHR1 mediates p53 transcription induced by high altitude hypoxia through ERK 1/2 signaling in rat hepatic cells. Peptides. 2013, 44(6): 8-14. PubMed ID: 23538210
   
   

   Dates from this article provide new evidence that the CRHR1-triggered ERK 1/2 pathway takes part in the activation of p53 and suppression of the apoptotic bax gene by hypoxia in rat liver.

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Reference

1. Bonfiglio J. J.; et al. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved. Neuroendocrinology. 2011, 94(1): 12-20.

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