NMBR Membrane Protein Introduction

Introduction of NMBR

NMBR, also known as NMB-R, bombesin receptor 1, epididymis secretory sperm binding protein Li 185a, BB1R, or BB1, is a 7-transmembrane G protein-coupled receptor (GPCR) composed of 390 amino acids, with a molecular weight of 43.4 kDd. In humans, it contains 3 exons and encoded by the NMBR gene which is mapping to the chromosome 6q24.1. NMBR is a member of GPCR I family and has three potential sites for N-glycosylation. Its products are known to bind an endogenous ligand neuromedin B (NMB). NMBR and GRPR share 55% amino-acid identity and have consistent protein kinase C phosphorylation sites in cytoplasmic loops and C-terminal domains. Also, they both have a similar gene structure, which suggests NMBR and GRPR evolve from a common ancestor. And human NMBR shares 89% sequence homology with rodent NMBR.

Function of NMBR Membrane Protein

NMBR possibly involves in the neuronal response, smooth muscle contraction, and regulation of cell growth. Its antagonist has a potential therapeutic role in inhibiting tumor cell growth. NMBR is a preferred receptor for NMB and binds to it with a high affinity. NMB is a growth factor and potent mitogen for the normal and neoplastic lung, as well as for the gastrointestinal epithelial tissue. It is implicated in human thyroid disorder and its mRNA is found to be expressed in central nervous systems and gastrointestinal tracts. In rat brains, NMB level is prominent in the dentate gyrus and olfactory bulb, and moderate expression is detectable in wider areas. NMB can regulate smooth muscle contraction, exocrine and endocrine secretion, grooming and scratching, blood glucose, energy homeostasis, body temperature, food intake, emotion, nociception, and cell growth. Remarkably, NMBR is expressed in a variety of human tumors and carcinoid tumors and may have a growth effect.

Fig.1 Distribution of NMBR in Leydig cells of the testes. (Ma, 2018)

Application of NMBR Membrane Protein in Literature

1. Mo C., et al. Characterization of NMB, GRP and their receptors (BRS3, NMBR and GRPR) in chickens. J Mol Endocrinol. 2017, 59(1), 61-79. PubMed ID: 28500250
   
   

   This paper aimed to characterize cNMB, cGRP and their receptors of cNMBR, cGRPR and cBRS3 in chickens. In conclusion, their data can help to uncover the roles of GRP, NMB and their receptors in birds and firstly provided persuasive evidence from an evolutionary perspective that GRP and NMB were the endogenous ligands for BRS3 in vertebrates.

2. Yeo C.E., et al. Neuromedin B and its receptor silencing suppresses osteoclast generation by modulating precursor proliferation via M-CSF/c-Fms/D-type cyclins. Exp Cell Res. 2017, 359(1), 112-119. PubMed ID: 28780306
   
   

   The study reported that NMB expression was upregulated during the osteoclast development and silencing NMB or NMBR can attenuate the osteoclast generation mediated by M-CSF and RANKL. Together, NMB/NMBR axis played a key role in osteoclast generations by regulating the proliferation and survival of osteoclast cells.

3. Ma Z., et al. Neuromedin B and its receptor: gene cloning, tissue distribution and expression levels of the reproductive axis in pigs. PLoS One. 2016, 11(3), e0151871. PubMed ID: 27010315
   
   

   To investigate the physiological functions of NMB, authors cloned and analyzed NMB and NMBR genes, and systematically research mRNA expressions of NMB and NMBR by using relative real-time PCR (RT-PCR) and the distribution of NMBR by operating immunohistochemistry (IHC).

4. Porcelli S., et al. PDE7B, NMBR and EPM2A variants and schizophrenia: a case-control and pharmacogenetics study. Neuropsychobiology. 2016, 73(3), 160-168. PubMed ID: 27092952
   
   

   The preliminary findings of this review suggested a possible role of NMBR and EPM2A genes in schizophrenia (SCZ) susceptibility and, for the second one, EPM2A may also play a part in antipsychotic pharmacogenetics. However, further research was required to confirm their findings.

5. Park H.J., et al. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Int J Oncol. 2016, 49(3), 934-942. PubMed ID: 27571778
   
   

   Neuromedin B (NMB) functioned as an autocrine growth factor as well as a pro-angiogenic factor. Its receptor, NMB receptor (NMBR), was overexpressed in solid tumors. In present studies, authors displayed that PD168368, an NMBR antagonist, repressed the migration and invasion of the human breast cancer cell line (MDA-MB-231).

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Reference

1. Ma Z, et al. (2018). Effects of neuromedin B on steroidogenesis, cell proliferation and apoptosis in porcine Leydig cells. J Mol Endocrinol. 61(1), 13-23.

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