THE EXPRESSION OF 2 SPLICE VARIANTS OF METABOTROPIC GLUTAMATE-RECEPTOR SUBTYPE-5 IN THE RAT-BRAIN AND NEURONAL CELLS DURING DEVELOPMENT

We previously reported that a variant with extra amino acid residues e xists in the metabotropic glutamate receptor subtype 5 (mGluR5). Eithe r of the two isoforms, named mGluR5b and mGluR5a for the isoforms with and without the inserted sequence, respectively, generated Ca2+-activ ated Cl- current when expressed in Xenopus oocytes. We herein report t hat these two isoforms are produced by the alternative splicing of the exon skipping type, When examined during the course of postnatal deve lopment, the major mGluR5 isotype mRNA was observed to switch from mGl uR5a to mGluR5b in the rat hippocampus and the cerebral cortex, We als o investigated two cell lines that could be differentiated into neuron -like cells in vitro, Whereas the mGluR5b mRNA was hardly detectable i n either undifferentiated or differentiated NG108-15 cells, the relati ve amounts of the two variant mRNAs changed after the induction of dif ferentiation in the P19 cells, An extracellular application of trans-D ,L-1-amino-1,3-cyclopentanedicarboxylate on the neuron-like P19 cells induced intracellular Ca2+ mobilization, thus suggesting that the cell s could express functional mGluR(s) coupled to phospholipase C and oth er components that could mediate the signal transduction pathway. This cell line may thus provide a model system for studying both mGluR5 ex pression and other mGluR-induced phenomena at the molecular level.