Metabotropic glutamate receptor 2

Neuroscience

Receptor

Biology

Metabotropic receptor

Chemistry

Metabotropic glutamate receptor 1

Metabotropic glutamate receptor 8

Metabotropic glutamate receptor

Metabotropic glutamate receptor 6

Computational biology

Metabotropic glutamate receptor 5

Genetics

Glutamate receptor

Metabotropic glutamate receptor 7

Cell Reports

The eight metabotropic glutamate receptors (mGluRs) serve critical modulatory roles throughout the nervous system. The molecular diversity of mGluRs is thought to be further expanded by the formation of heterodimers, but the co-expression of mGluR subtypes at the cellular level and the relative propensities of heterodimer formation are not well known. Here, we analyze single-cell RNA sequencing data and find that cortical pyramidal cells express multiple mGluR subtypes with distinct profiles for different receptor combinations. We then develop quantitative, fluorescence-based assays to define the relative homo- and heterodimer propensities across group-I, -II, and -III mGluRs. We find a strong preference for heterodimerization in a number of cases, including mGluR2 with mGluR3, which we confirm in frontal cortex using in situ RNA hybridization and co-immunoprecipitation. Together, our findings support the biological relevance of mGluR heterodimerization and highlight the complex landscape of mGluR populations in the brain.

Defining the Homo- and Heterodimerization Propensities of Metabotropic Glutamate Receptors