Glutamate receptor

Glutamate receptors are transmembrane proteins in the membrane of neurons, which specifically bind the neurotransmitter glutamate. Especially great is their density at the postsynaptic membrane of glutamatergic synapses. Within the group of glutamate receptors are divided into ionotropic and metabotropic glutamate receptors.

Ionotropic glutamate receptors

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

AMPA receptors are tetrameric ion channels that are permeable to sodium and potassium ions. Depending on what protein subunits they are composed, they may have a calcium -type conductivity.

NMDA receptors are non-selective cation channels tetramers, in addition to the ligand-dependent activation also show a voltage dependence. The opening of the NMDA receptor channel requires not only the binding of glutamate, but also the elimination of its blockage by each a magnesium ion in depolarization of the postsynaptic membrane.

Kainate receptors are tetrameric ion channels which are conductive in the first place to sodium and potassium, but also a little calcium. Calcium conductance depends mainly on the editing new subunits.

Metabotropic glutamate receptors

The metabotropic glutamate receptors belong to the phylogenetically oldest G- protein-coupled receptors. Currently, eight metabotropic glutamate receptors are known: mGlu1 to mGlu8 ( mGluR1 - mGluR8 ). Because of similarities in the amino acid sequence, pharmacological properties and intracellular signaling pathways by which they are linked, they are divided into three groups. Group I: ( Gq - coupled ) This includes mGluR1 and mGluR5. Activate phospholipase C, resulting in the accumulation of IP3 and diacylglycerol (DAG ) in the cell interior. IP3 receptors on it comes to the release of calcium ions from the endoplasmic reticulum, while DAG activates protein kinase C, especially. Group II: ( Gi- coupled ) This includes mGluR2 and mGluR3. They regulate the adenylate cyclase negative. Group III: ( Gi- coupled ) This includes mGluR4, mGluR6, mGluR7 and mGluR8. As the group II mGluR they inhibit adenylate cyclase. They all share a large N- terminal domain, on which the glutamate - binding site is located.

GLUD2 ( GluRδ2 ) receptors

A special role is the so-called " orphan" a (English for " orphan " ) glutamate receptors of type GLUD2 (or " GluRδ2 "). This term is expressed, that the subunits of this receptor have no relationship with the other known glutamate receptors, and, with this no functional heteromeric receptors. The GLUD2 subunit is expressed exclusively in Purkinje cells of the cerebellum. The binding of glutamate to GLUD2 is essential for the normal function of the Purkinje cells and thus of the cerebellum. The ligand of the receptor in the cerebellum GLUD2 Cbln1 is a soluble protein that is released from the granule cells in the cerebellar cortex. It binds to the extracellular N -terminus of GLUD2 to Purkinje cells. Which has two independent consequences: first, it leads to presynaptic differentiation and secondly, it causes the common storage of different molecules that are essential for synaptic function. Both events are necessary for the formation of synapses between grains and Purkinje cells.