Glutamate receptor

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Glutamate receptor
Transporter classification
TCDB 1.A.10
designation glutamate-gated ion channel neurotransmitter receptors

Glutamate receptors are transmembrane proteins in the membrane of neurons that specifically bind the neurotransmitter glutamate . Their density on the postsynaptic membrane of glutamatergic synapses is particularly high . Within the group of glutamate receptors, a distinction is made between ionotropic and metabotropic glutamate receptors.

Ionotropic glutamate receptors

The ionotropic glutamate receptors include AMPA receptors , NMDA receptors, and kainate receptors . They differ in their structure, the sequence of their subunits and their specific binding, activation and conduction properties.
All three are highly affine for glutamate and have different preferences for other glutamate agonists such as the named substances AMPA ( English α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ), NMDA ( N -methyl- D -aspartate) and Kainat .

AMPA receptors are tetrameric ion channels , for the permeable sodium - and potassium - ions are. Depending on from which protein subunits are assembled, they can also be a calcium - conductivity have.

NMDA receptors are tetrameric, nonselective cation channels which, in addition to ligand-dependent activation, also show a voltage dependence . The opening of the NMDA receptor channel not only requires the binding of glutamate, but also the removal of its blockage by a magnesium ion each when the postsynaptic membrane is depolarized .

Kainate receptors are tetrameric ion channels that are primarily conductive for sodium and potassium, but also a little for calcium. The calcium conductivity depends mainly on the editing of the subunits.

Metabotropic glutamate receptors

The metabotropic glutamate receptors are among the phylogenetically oldest G protein-coupled receptors . Eight metabotropic glutamate receptors are currently known: mGlu 1 to mGlu 8 (mGluR1 - mGluR8). Based on similarities in the amino acid sequence , pharmacological properties, and intracellular signaling pathways with which they are coupled, these are divided into three groups.
Group I: (G q -coupled) These include mGluR1 and mGluR5 . They activate phospholipase C , which leads to the accumulation of IP 3 and diacylglycerol (DAG) inside the cell. About IP 3 receptors it comes to the release of calcium ions from the endoplasmic reticulum , whereas DAG especially the protein kinase C activates.
Group II: (G i -coupled) These include mGluR2 and mGluR3 . They negatively regulate adenylate cyclase .
Group III: (G i- coupled) These include mGluR4 , mGluR6 , mGluR7 and mGluR8 . Like group II mGluR, they inhibit adenylate cyclase.

What they all have in common is a large N-terminal domain on which the glutamate binding site is located.

GluD2 (GluRδ2) receptors

The so-called " orphan " (or "orphan") glutamate receptors of the GluD2 (or "GluRδ2") type occupy a special position . This designation expresses that the subunits of this receptor are not related to the other known glutamate receptors and do not form functional heteromeric receptors with them. The GluD2 subunit is expressed exclusively in Purkinje cells of the cerebellum . The binding of glutamate to GluD2 is an indispensable prerequisite for the normal function of the Purkinje cells and thus the cerebellum. The ligand of the GluD2 receptor in the cerebellum is Cbln1 , a soluble protein released by the granule cells in the cerebellar cortex. It binds to the extracellular N -terminus of GluD2 on Purkinje cells. This has two independent consequences: first, it leads to presynaptic differentiation and, second, it causes the aggregation of different molecules that are important for synaptic function. Both events are necessary for synapse formation between granule and Purkinje cells.

Receptor modulators

The synthetic active ingredients NBQX and 2-amino-5-phosphonovaleric acid are glutamate receptor antagonists.

literature

  1. ↑ K. Matsuda, E. Miura, T. Miyazaki, W. Kakegawa, K. Emi, S. Narumi, Y. Fukazawa, A. Ito-Ishida, T. Kondo, R. Shigemoto, M. Watanabe, M. Yuzaki : Cbln1 Is a Ligand for an Orphan Glutamate Receptor 2, a Bidirectional Synapse Organizer. In: Science . 328, 2010, p. 363, doi : 10.1126 / science.1185152 .
  2. ^ MJ Sheardown: The pharmacology of AMPA receptors and their antagonists. In: Stroke . Volume 24, Number 12 Suppl, December 1993, pp. I146-1147, ISSN  0039-2499 . PMID 7504337 .
  3. ^ RG Morris: Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. In: The Journal of neuroscience: the official journal of the Society for Neuroscience. Volume 9, Number 9, September 1989, pp. 3040-3057, PMID 2552039 .

Web links

Structure of glutamate receptors