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

- Metabotropic glutamate receptor 1 (mGluR1) is expressed in several splice variants.
- Alternative splicing of mGluR1 results in complexes in which variants may combine.
- mGluR1b variant is found mainly in association with mGluR1a in mGluR1a/b complexes.
- Long mGluR1a is required for proper mGluR1b trafficking within the mGluR1a/b complex.

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.

The mGluR1a/b heterodimers are trafficked to distal dendrites and have a similar pattern of distribution as mGluR1a homodimers within neurons, while mGluR1b homodimers are retained in cell bodies, presumably within Endoplasmic Reticulum.