GRIN3B Membrane Protein Introduction

Introduction of GRIN3B

The Glutamate receptor ionotropic, NMDA 3B (GRIN3B) subunit, also called NR3B, is a newly identified subunit of the N-methyl-d-aspartate (NMDA) receptors. It was initially discovered in 1995 but was not completely characterized until 2003. Conventional NMDARs contain the GRIN1 and GRIN2 subunits, while the incorporation of GRIN3 (GRIN3A and GRIN3B) forms triheteromers or diheteromers that exhibit properties different from conventional GRIN1/GRIN2 receptors. GRIN3B, together with GRIN3A, bind glycine rather than glutamate, which is a property very much like GRIN1. As a result, GRIN1/GRIN3 NMDA receptors only require glycine for activation. The expression pattern of GRIN3B is under spatial and temporal control. GRIN3B mRNA expression levels are elevated through the development and maintained into adulthood, with a distribution in the pons, midbrain, medulla and spinal cord.

Functions of GRIN3B Membrane Protein

The incorporation of GRIN3B subunit into the NMDARs results in reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. To study the physiological roles of GRIN3B subunits, genetic ablation of the GRIN3B gene in mouse has successfully led to the generation of GRIN3B knockout mice. Phenotypically, these mice are fertile and grow to adulthood without apparent behavioral abnormalities. However, they show moderate but significant impairment in motor learning/coordination and decreased activity in their home cages. Besides, they also display increased social behavior in the familiar cage but moderately increased anxiety-like behavior with decreased social interaction in a new environment. A null-allele in human GRIN3B caused by a 4-bp insertion (insCGTT) leads to truncation of the GRIN3B polypeptide within the amino-terminal domain, which may be a risk factor for schizophrenia.

Fig.1 NMDA subunit structure and topology.

Application of GRIN3B Membrane Protein in Literature

1. Matsuno H., et al. A naturally occurring null variant of the NMDA type glutamate receptor NR3B subunit is a risk factor of schizophrenia. PLoS One. 2015, 10(3): e0116319. PubMed ID: 25768306
   
   

   This study investigated the significance of a common human genetic variation of the GluN3B subunit of NMDAR that inserted 4 bases within the coding region (insCGTT) in the pathogenesis of schizophrenia. The results of this study indicated that this variant of the GluN3B subunit could be a risk factor for schizophrenia.

2. de Jesus Domingues A.M., et al. Identification of four functional NR3B isoforms in developing white matter reveals unexpected diversity among glutamate receptors. Journal of neurochemistry. 2011, 117(3): 449-460. PubMed ID: 21320125
   
   

   This study investigated the expression of several NMDA receptor subunits (GluN1, GluN2B-C, GluN3A-B) in the brain and optic nerve by molecular cloning. Four GluN3B variants generated by alternative splicing were identified.

3. Wee K.S.L., et al. The distal carboxyl terminal of rat NR3B subunit regulates NR1-1a/NR3B and NR1-2a/NR3B surface trafficking. Neurochemistry international. 2010, 57(2): 97-101. PubMed ID: 20466026
   
   

   This study investigated the role of a conserved RERLR motif in the distal carboxyl terminal of the rat NR3B in targeting NR1-1a/NR3B and NR1-2a/NR3B receptors to the surface.

4. Sedaghati M., et al. Expression of NR3B but not NR2D subunit of NMDA receptor in human blood lymphocytes can serve as a suitable peripheral marker for opioid addiction studies. European journal of pharmacology. 2010, 633(1-3): 50-54. PubMed ID: 20153313
   
   

   This article measured the mRNA expression of NR3B and NR2D in four groups of individuals: opioid addicts, methadone-maintained patients, long-term abstinent former opioid addicts, and non-addicted control subjects. The mRNA expression of NR3B was significantly elevated, indicating that the level of this subunit can serve as a suitable marker for opioid addiction studies.

5. Fukumori R., et al. Requirement of both NR3A and NR3B subunits for dominant negative properties on Ca²⁺ mobilization mediated by acquired N-methyl-D-aspartate receptor channels into mitochondria. Neurochemistry international. 2010, 57(7): 730-737. PubMed ID: 20813147
   
   

   This study investigated Ca(2+) influx across acquired NMDAR channels composed of different NR subunits artificially expressed in HEK293 cells. The authors found that co-expression of both the NR3A and NR3B subunits was essential for the dominant negative properties on Ca(2+) mobilization through acquired functional NMDAR channels into mitochondria.

GRIN3B Preparation Options

Supported by our powerful Magic™ Membrane Protein Production Platform, Creative Biolabs offers solutions to the challenge of the production of difficult-to-prepare membrane proteins. Among our various approaches, detergents are the first options for membrane protein solubilization, stabilization, and isolation. The choice of detergent is crucial to preserve the integrity of the membrane protein complex.

Alternative strategies that provide a more stable environment for the proteins include the proteoliposomes and nanodisc technology. Moreover, the use of polymers is another newly developed detergent-free method that effectively extracts the protein yet retain structure and stability. Virus-like particle technology prepares membrane proteins in lipoparticles that are suitable for anti-membrane protein antibody discovery. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GRIN3B antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Based on our experience, Creative Biolabs can always give professional advice on the selection of the optimal approaches for your project purposes. Contact us to get full advice from our experts for your membrane protein preparation.

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