GRIN2D Membrane Protein Introduction

Introduction of GRIN2D

Glutamate receptor ionotropic, NMDA 2D (GRIN2D), is a subunit of the NMDA receptors. NMDA receptors are typically composed of two glycine-binding GRIN1 subunits and two glutamate-binding GRIN2 subunits. The GRIN2 subunits have four members, GRIN2A-2D, which confer distinct properties to the receptor. Here, we give an introduction to the GRIN2D subunit. Structurally, GRIN2D is composed of four discrete semiautonomous domains, including the extracellular amino-terminal domain (ATD), extracellular ligand-binding domain (LBD), transmembrane domain (TMD), and intracellular carboxyl-terminal domain (CTD). Especially, GRIN2D-containing NMDA receptors have a strikingly slow deactivation time course, low single-channel open probability, and weak magnesium sensitivity compared with the other GRIN2 subunits. In terms of expression patterns, GRIN2D is present early in development and is strongest in the diencephalon, mesencephalon and spinal cord in adulthood.

Functions of GRIN2D Membrane Protein

As a subunit of NMDARs, GRIN2D is implicated in neuronal development, synaptic plasticity, and learning and memory. Dysfunction or deficiency of this subunit is also involved in various psychiatric disorders. For instance, transcripts that encoded GRIN2D are reduced in relay neurons in the medial dorsal thalamus in schizophrenia. Moreover, studies in GRIN2D knockout mice have shown that this subunit plays an essential role in the effects of phencyclidine (PCP) and UBP141, which are antagonists of NMDARs. Additionally, the GRIN2D subunit is found critical for the sustained antidepressant effects of (R)-ketamine. Loss of GRIN2D subunit in mice results in social recognition deficit, social stress, and anhedonia. Besides, GRIN2D might constitute an attractive target for developing therapeutic interventions for Parkinson’s disease.

Fig.1 NMDA subunit structure and topology. (Sanz-Clemente, 2013)

Application of GRIN2D Membrane Protein in Literature

1. Swanger S.A., et al. NMDA receptors containing the GluN2D subunit control neuronal function in the subthalamic nucleus. Journal of Neuroscience. 2015, 35(48): 15971-15983. PubMed ID: 26631477
   
   

   This study investigated how GluN2D-containing NMDA receptors mediated excitatory synaptic transmission in the subthalamic nucleus (STN) and tested whether modulating of these receptors influenced STN spike firing in vivo. The results suggested GluN2D-containing NMDAR had therapeutic potential in the regulation of STN spike activity.

2. Zhang X., et al. GluN2D-containing NMDA receptors inhibit neurotransmission in the mouse striatum through a cholinergic mechanism: implication for Parkinson's disease. Journal of neurochemistry. 2014, 129(4): 581-590. PubMed ID: 24475872
   
   

   Using amperometry and field potential recordings in mouse brain slices, this article investigated the role of GluN2D-containing NMDARs in dopamine release and glutamatergic neurotransmission in the mouse striatum. Also, the function of these receptors in the mouse model of Parkinson’s disease (PD) was examined. The results showed that GluN2D might constitute an attractive target for therapeutic intervention development for PD.

3. Sapkota K., et al. GluN2D N-methyl-d-aspartate receptor subunit contribution to the stimulation of brain activity and gamma oscillations by ketamine: implications for schizophrenia. Journal of Pharmacology and Experimental Therapeutics. 2016, 356(3): 702-711. PubMed ID: 26675679
   
   

   In this study, to evaluate the contribution of GluN2D subunit to antagonist-induced cortical activation and schizophrenia symptoms, the ability of ketamine to alter regional brain activity and gamma frequency band neuronal oscillations in both wild-type and GluN2D-deficient mice was investigated. The results suggested a critical role of GluN2D subunits in cognition and perception.

4. Dubois C.J., et al. Presynaptic GluN2D receptors detect glutamate spillover and regulate cerebellar GABA release. Journal of neurophysiology. 2015, 115(1): 271-285. PubMed ID: 26510761
   
   

   To determine whether tri-heteromeric GluN2B/2D NMDA receptors mediated long-term potentiation of inhibitory transmission, this study tested the prediction that deletion of GluN2D converted tri-heteromeric GluN2B/2D to di-heteromeric GluN2B NMDA receptors in GluN2D-knockout mice.

5. Hildebrand M.E., et al. GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord. Scientific reports. 2014, 4: 4094. PubMed ID: 24522697
   
   

   This study investigated the role of GluN2B and GluN2D subunit in mediating synaptic NMDAR responses in adult lamina I neurons. The charge transfer mediated by GluN2D far exceeds that of GluN2A and was comparable to that of GluN2B.

GRIN2D Preparation Options

The molecular mechanisms and involvement in physiological processes of NMDAR receptor subunits like GRIN2D have not been fully characterized for further therapeutics development. To promote your research of membrane proteins, Creative Biolabs introduces our powerful Magic™ Membrane Protein platform to obtain their protein of interest in the stabilized, purified, functional formats, including detergent micelles, liposomes, nanodiscs, polymers, etc. Besides, VLP-derived lipoparticle is another alternative for membrane protein incorporation. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GRIN2D antibody development services.

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Reference

1. Sanz-Clemente A, et al. (2013). Diversity in NMDA receptor composition: many regulators, many consequences. The Neuroscientist. 19(1): 62-75.

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