Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone

Abstract

The probability of synaptic neurotransmitter release from nerve terminals is regulated by presynaptic receptors responding to transmitters released from the same nerve terminal or from terminals of other neurons. The release of glutamate, the major excitatory neurotransmitter, is suppressed by presynaptic autoreceptors. Here we show that a metabotropic glutamate receptor (mGluR7) in the rat hippocampus is restricted to the presynaptic grid, the site of synaptic vesicle fusion. Pyramidal cell terminals presynaptic to mGluR1alpha-expressing interneurons have at least a ten-fold higher level of presynaptic mGluR7 than terminals making synapses with pyramidal cells and other types of interneuron. Distinct levels of mGluR7 are found at different synapses made by individual pyramidal axons or even single boutons. These results raise the possibility that presynaptic neurons could regulate the probability of transmitter release at individual synapses according to the postsynaptic target.

Surface expression of metabotropic glutamate receptor variants mGluR1a and mGluR1b in transfected HEK293 cells

“…Results are expressed as the amount of IP produced over the radioactivity present in the membranes. (rabbit) raised against synthetic peptides linked to thyreoglobulin (mGluR1a derived epitope CTPPNVTYASVILRDYKQSSSTL-COOH) and O13 (guinea pig) generated against epitope derived from mGluR1b sequence (KRQPEFSPSSQCPSAHAQL-COOH) were used in dilution 1:500 (Mateos et al, 1998;Petralia et al, 1997;Shigemoto et al, 1996). Secondary antibodies were used in dilutions:…”

Regulation of Metabotropic Glutamate Receptor 7 (mGluR7) Internalization and Surface Expression by Ser/Thr Protein Phosphatase 1

“…Among the mGluR family, mGluR7 belongs to the group III mGluRs, which are coupled to inhibitory G proteins. Group III mGluRs are often presynaptic (2,3), and mGluR7 is highly expressed at the presynaptic active zone throughout the CNS and acts as an auto-regulatory receptor. Because of its low affinity for glutamate, mGluR7 has been proposed to be only activated under conditions of sustained synaptic activity and play a role in feedback inhibition to limit further release of glutamate at excitatory synapses (4,5).…”

Group I Metabotropic Glutamate Receptors Bind to Protein Phosphatase 1C

“…mGluR2 and mGluR3 (group II) are negatively coupled to adenylyl cyclase and do not show a specific preference for pre-or postsynaptic neurons (8 -10). mGluR4, mGluR7, and mGluR8 (group III) are also negatively coupled to adenylyl cyclase and are primarily found at the active zone where they are suggested to function as glutamate auto-receptors (10,(11)(12)(13)(14)(15)(16). Of the group III mGluRs the expression of mGluR6 is restricted to the retina, where it is localized postsynaptically at retinal photoreceptor to bipolar cell synapses, transmitting the "light on" signal in visual signal transduction (17, 18).…”