Metabotropic glutamate receptor 1 splice variants mGluR1a and mGluR1b combine in mGluR1a/b dimers in vivo

Abstract

The assembly of two covalently linked monomers into dimeric complexes is a prerequisite for metabotropic glutamate receptor 1 (mGluR1) function. The former concept of a strictly homodimeric subunit contribution in metabotropic glutamate receptor complexes has recently been brought into question. Alternative splicing of the GRM1 gene results in expression of variants that vary within their intracellular C-termini. Here we bring evidence that the short mGluR1b variant is found preferentially in a complex with the long mGluR1a variant in the rodent brain. The mGluR1a and mGluR1b variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines. However mGluR1a and mGluR1b show distinct sub-cellular localization when expressed alone in neurons. We discovered that trafficking of mGluR1b to distal dendrites is reliant on its association with mGluR1a and that the long C-terminus of mGluR1a within the mGluR1a/b dimer is necessary for trafficking of the complex.

Prenatal valproate treatment produces autistic-like behavior and increases metabotropic glutamate receptor 1A-immunoreactivity in the hippocampus of juvenile rats

“…In base to these results, the present study failed to determine the origin of increased mGluR1a immunoreactivity, but suggested an over-functioning of that specific type of class I mGluR, in line with the previous evidence for the involvement of this family of receptors in autism. Analysis of mRNA is required and it is interesting to determinate mGluR1a and mGluR1b levels since an interesting cooperative function between 1a and 1b isoforms has been previously demonstrated (57). In addition, the present study cannot discard the role of mGluR5 in the VPA model of autism and the possible cooperative signaling between homodimers of metabotropic glutamate receptors 1 and 5 is highly interesting (58).…”

The Class-A GPCR Dopamine D2 Receptor Forms Transient Dimers Stabilized by Agonists: Detection by Single-Molecule Tracking

“…Despite the importance of GPCRs, the fundamental question of whether GPCRs form and work as monomers, dimers, and/or greater multimers have remained unanswered [ 1 – 16 ]. The functional units of class-C GPCRs, including metabotropic glutamate receptor 1 [ 17 – 21 ] and GABA B receptors [ 22 – 24 ], are generally considered to be constitutive homo- and/or hetero-dimers. However, our knowledge about the oligomeric states of the largest class of GPCRs, the class-A group GPCRs, is quite limited.…”

Group 1 metabotropic glutamate receptors 1 and 5 form a protein complex in mouse hippocampus and cortex

“…Group1 metabotropic glutamate receptors are G‐protein coupled receptors comprising the closely related mGluR1 (GRM1) and 5 (GRM5), where mGluR1 exists in two isoforms differing only at the C‐termini due to alternative splicing of the gene . Metabotropic GluR5 is primarily localized at the postsynapse, where it regulates short‐ and long‐term synaptic plasticity, in particular long‐term depression .…”