The C-terminus of the metabotropic glutamate receptor 1b regulates dimerization of the receptor.
The Group C G protein-coupled receptors include the metabotropic glutamate receptors (mGluRs), the GABA(B) receptor, the calcium sensor and several taste receptors, most of which are obligate dimers, indeed recent work has shown that dimerization is necessary for the activation of these receptors. Consequently factors that regulate their ability to homo- or heterodimerize are important. The Group 1 mGluRs include mGluR1 and mGluR5 both of which have splice variants with altered C-termini. In this study, we show that mGluR1b is a dimer and that it does not efficiently heterodimerize with mGluR1a, unlike the two splice variants of mGluR5 that can heterodimerize. Mutation of a positively charged motif (RRKK) at the C-terminus of the mGluR1b tail permits mGluR1b to heterodimerize with mGluR1a. Co-expression of mGluR1a and mGluR1b in COS-7 cells results in the accumulation of mGluR1b in intracellular inclusions that do not contain mGluR1a. This behaviour is mimicked by a chimera of the lymphocyte antigen CD2 with the C-terminus of mGluR1b (pCD1b) and depends on the presence of the RRKK motif. These accumulations are immunoreactive for endoplasmic reticulum (ER) markers, but not Golgi and ERGIC markers. This segregation of mGluR1b from other ER proteins may contribute to its failure to dimerize with mGluR1a.
Remelli
Rosaria
R
Medical Research Council Anatomical Neuropharmacology Unit, Oxford, UK.
Robbins
Melanie J
MJ
McIlhinney
R A Jeffrey
RA
D000818:Animals; D019556:COS Cells; D002531:Cerebellum / Q000502:physiology; D002522:Chlorocebus aethiops; D019281:Dimerization; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D010446:Peptide Fragments; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1