The cell surface expression of metabotropic glutamate receptor type 1 splice variants has been studied using cell surface biotinylation. Go-expression of the last 86 residues of the C-terminal tail of mGluR1 alpha (F2-protein) with mGluR1 alpha caused a significant reduction of the amount of the cell surface receptor when compared to that in cells transfected with mGlur1 alpha alone, and this was accompanied by a reduction in the production of inositol following agonist stimulation of the cells. In contrast, cell surface expression of mGluR1 beta was unaltered by co-expression with the F2-protein. These results suggest that the C-terminal tail of mGluR1 alpha regulates cell surface expression of the receptor. (C) 1999 Federation of European Biochemical Societies.