Grm1

Official Full Name

glutamate receptor, metabotropic 1

Organism

Mus musculus

GeneID

14816

Background

Enables G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration and G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential. Involved in several processes, including positive regulation of MAPK cascade; regulation of sensory perception of pain; and synaptic signaling via neuropeptide. Acts upstream of or within L-glutamate import across plasma membrane and cellular response to electrical stimulus. Located in dendrite; nucleus; and postsynaptic density. Is active in Schaffer collateral - CA1 synapse and glutamatergic synapse. Is expressed in several structures, including appendicular skeleton; eye; nervous system; testis; and tongue. Used to study autosomal recessive spinocerebellar ataxia 13; skin melanoma; and uveal melanoma. Human ortholog(s) of this gene implicated in autosomal recessive spinocerebellar ataxia 13 and spinocerebellar ataxia 44. Orthologous to human GRM1 (glutamate metabotropic receptor 1). [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

Grm1; rcw; wobl; Gprc1a; mGluR1; nmf373; Gm10828; 4930455H15Rik;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

Metabotropic glutamate receptor 1 (mGluR1), the protein product of the GRM1 gene, is a Family C G protein-coupled receptor (GPCR) belonging to Group I of mGluRs, along with mGluR5. Apart from the seven transmembrane helical structures, conserved throughout all GPCRs, Class C receptors are also characterized by a large bi-lobed ligand binding domain linked to the transmembrane region by a cysteine-rich domain, as well as a large intracellular C-terminal tail. GRM1 is commonly expressed in the central nervous system where they mediate neuronal excitability and neurotransmitter release.

Pharmacological activation of mGluR1, resulting in activation of phospholipase C and consequent phosphoinositide hydrolysis, has been suggested to facilitate NMDA receptor responses in cortical neurons and the CA3 area of the hippocampus. The receptor also plays an important role in synaptic plasticity, memory and learning by regulating local dendritic protein synthesis in functional interaction with the fragile X mental retardation protein (FMRP). Hypofunction/dysregulation of glutamatergic signaling is one of the dominant concepts of schizophrenia pathogenesis, originally based on observations that NMDA receptor antagonists can induce psychotic symptoms and cognitive deficits closely resembling those in schizophrenia, and later supported by findings of altered NMDA receptor subunit composition and changes in NMDA receptor-related postsynaptic proteins in schizophrenia brains.

GRM1 and melanoma

Glutamate signaling through mGluR1 has been shown to affect cell survival, cell proliferation and cell differentiation of non-neuronal tissues. A link between mGluR1 and cancer was serendipitously discovered when the creation of a transgenic mouse for a different purpose unexpectedly led to a transgenic strain in which melanoma formation developed at high penetrance at a young age. In this transgenic strain, melanoma formation was also associated with the overexpression of mGluR1. So far, ~175 melanoma biopsy samples from primary to metastatic lesions have been examined and found GRM1 mRNA and protein to be expressed in ~ 60% of the samples. In addition, expression and activation of mGluR1 in melanoma cells has been shown to activate the MAPK and P13K/AKT pathways, two of the most frequently stimulated signaling cascades in melanoma.

GRM1 and breast cancer

About 15-20% of breast cancers do not express hormone receptors or amplify human epidermal growth factor receptor 2 (HER2). Although it is heterogeneous, this form of breast cancer, dubbed “triple negative breast cancer” (TNBC), shows considerable overlap with the “basal-like” subtype and tends to be the most aggressive form with the poorest prognosis. The preclinical evidence strongly shows that mGluR1 plays a significant role in mediating the growth and progression of TNBC, beginning with the detection of expression and functional activity of mGluR1 in various TNBC cells as demonstrated by their ability to regulate cell growth and survival via signaling through the Akt pathway. The inhibitors of glutamatergic signaling block TNBC cell proliferation in a time- and dose-dependent manner correlating with increased apoptosis in vitro. These same compounds are also effective against MDA-MB-231 xenografts in mice, which express mGluR1. One of these inhibitors, riluzole, is a glutamate release inhibitor in current clinical use that is FDA-approved for amyotrophic lateral sclerosis. Thus, these studies suggest that mGluR1 can interact with other factors to promote progression in hyperplastic mammary epithelium and therefore represents a potentially promising therapeutic target in TNBC.

References:

Martino J J, et al. Metabotropic glutamate receptor 1 (Grm1) is an oncogene in epithelial cells. Oncogene, 2013, 32(37):4366-4376.
Kaliki S, et al. Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer. Breast Cancer Research & Treatment, 2012, 132(2):565-573.
Banda M, et al. Metabotropic Glutamate Receptor-1 Contributes to Progression in Triple Negative Breast Cancer. PLoS ONE, 2014, 9(1):e81126.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry