MTNR1A Membrane Protein Introduction

Introduction of MTNR1A

MTNR1A, also known as melatonin receptor 1A, MEL-1A-R, MT1, is an approximately 39.4 kDa G protein-coupled and seven-transmembrane receptor. This protein consists of 350 amino acids and in humans, is encoded by MTNR1A gene mapping to the chromosome 4q35.2. MTNR1A codes for one of two high-affinity forms of the receptor for melatonin, a primary hormone released by pineal glands. And melatonin receptors are split into two subtypes containing MTNR1A and MTNR1B, which are widely detected both in the brain as well as in the retina with high concentrations. MTNR1A is an integral membrane protein that belongs to the G protein-coupled receptor (GPCR) superfamily. It is readily found and localized in two particular regions of the brain, including the hypothalamic suprachiasmatic nucleus and hypophysial pars tuberalis.

Function of MTNR1A Membrane Protein

As reported, the hypothalamic suprachiasmatic nucleus may be implicated in circadian rhythm while the hypophysial pars tuberalis appears to take charge of the reproductive effect on melatonin. Melatonin is able to alter the timing of mammalian circadian rhythms and regulates reproductive modifications occurred in response to changes in day length of seasonally breeding mammals. So, it is indicated that MTNR1A as a melatonin receptor is likely to mediate two main melatonin effects on mammalian circadian actions and reproductive alterations influenced by day length. Except that, this receptor has other agonists, involving afobazole and agomelatine. The activity of MTNR1A is modulated by pertussis toxin-sensitive G proteins which can inhibit adenylate cyclase activities. It has a number of associated pathways that are circadian rhythm-related genes and peptide ligand-binding receptors. There are several diseases related to MTNR1A mutations, including scoliosis and idiopathic scoliosis.

Fig.1 Subcellular localization analysis and the putative tertiary structure of AccMTNR1A from Apis cerana cerana. (Li, 2018)

Application of MTNR1A Membrane Protein in Literature

1. Calvo J.H., et al. SNP rs403212791 in exon 2 of the MTNR1A gene is associated with reproductive seasonality in the Rasa aragonesa sheep breed. Theriogenology. 2018, 113, 63-72. PubMed ID: 29475126
   
   

   The paper objective was to characterize and identify causative SNPs in the MTNR1A gene taking charge of the reproductive seasonality traits in the Rasa Aragonesa sheep breed. Authors had indicated that the T allele in the SNP rs403212791 of MNTR1A gene was correlated with a lower TDA and a higher P4CM and OCM value in this sheep breed.

2. Owino S., et al. Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of PI3K activity. J Pineal Res. 2018, 64(3). PubMed ID: 29247541
   
   

   The results demonstrated that the activation of MT1 signaling at night controls insulin sensitivity during the day by regulating the PI3K transcription and activity. And there was evidence that the reduced expression of MTNR1A (MT1) in the liver of diabetic cases was connected with poorly restrained diabetes.

3. Huang Y.S., et al. Role of melatonin receptor 1A and pituitary homeobox-1 coexpression in protecting tubular epithelial cells in membranous nephropathy. J Pineal Res. 2018, e12482. PubMed ID: 29480949
   
   

   Together, experimental data suggested that in injured tissues, decreased PITX1 level at the MTNR1A promoter regions resulted in reduced expressions of MTNR1A in renal tubular epithelial cells, which elevated the risk of Membranous nephropathy (MN) in the future.

4. Li G., et al. Identification of a melatonin receptor type 1A gene (AccMTNR1A) in Apis cerana cerana and its possible involvement in the response to low temperature stress. Naturwissenschaften. 2018, 105(3-4), 24. PubMed ID: 29569081
   
   

   In this study, the authors found an MTNR from Apis cerana cerana (AccMTNR1A), which contained a typical 7-transmembrane domain common to this receptor family. An analysis revealed that AccMTNR1A was localized in the cytomembrane. In addition, cold stress was found to apparently boost AccMTNR1A transcription, indicating AccMTNR1A may connect to the cold stress response.

5. Wang S.J., et al. The role of Melatonin receptor MTNR1A in the action of Melatonin on bovine granulosa cells. Mol Reprod Dev. 2017, 184(11), 1140-1154. PubMed ID: 28805353
   
   

   This article suggested that melatonin and MTNR1A played a critical role in modulating bovine granulosa cells (GCs) function by regulating cellular progress, such as apoptosis, hormones secretion, along with reproduction-related genes. Moreover, the altered expression of MTNR1A affected how bovine GCs responded to the melatonin.

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Reference

1. Li G, et al. (2018). Identification of a melatonin receptor type 1A gene (AccMTNR1A) in Apis cerana cerana and its possible involvement in the response to low temperature stress. Naturwissenschaften. 105(3-4), 24.

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