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Glutamate Receptors: NMDA and Delta Receptors

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract

N-methyl-d-aspartate (NMDA) receptors and delta (δ) receptors are members of the ionotropic glutamate receptor (iGluR) family, along with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and kainate receptors. Unlike AMPA receptors, both NMDA and δ receptors do not contribute to normal fast neurotransmission. Instead, the activity of these receptors regulates AMPA receptor trafficking and synaptic plasticity. The traditional function of NMDA receptors is achieved through their Ca2+ permeable channels. However, it has become increasingly clear that intracellular proteins that bind to the C-termini of NR2 subunits, and possibly those of NR3 subunits, play crucial roles in NMDA receptor trafficking and intracellular signaling, leading to specific gene expression. Similarly, recent studies have indicated that the δ2 glutamate receptor does not function as a channel, but as a non-ionotropic receptor that regulates intracellular signaling through its C-terminal interaction. Another feature common to both NMDA and δ2 receptors is their ability to bind to d-serine and glycine; these molecules are released from glial cells as “gliotransmitters” and regulate synaptic plasticity. Therefore, although the amino acid sequence similarity between the two receptor families is rather low, characterization of the signaling mechanisms underlying each family should add to the knowledge of each family, facilitating a better understanding of learning and memory.

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Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BDNF:

brain-derived neurotrophic factor

CaN:

calcineurin

CREB:

cyclic AMP responsive element-binding protein

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

iGluR:

ionotropic glutamate receptor

JNK:

c-Jun NH2-terminal kinase

LBD:

ligand-binding domain

LTD:

long-term depression

LTP:

long-term potentiation

MAPK:

mitogen-activated protein kinase

NMDA:

N-methyl-d-aspartate

NTD:

N-terminal domain

PF:

parallel fiber

PKC:

protein kinase C

PSD:

postsynaptic density

SynGAP:

synaptic Ras GTPase activating protein

TM1:

transmembrane domain 1

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  1. M. Yuzaki
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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Yuzaki, M. (2009). Glutamate Receptors: NMDA and Delta Receptors. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_16

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