Structural organization of the mouse metabotropic glutamate receptor subtype 3 gene and its regulation by growth factors in cultured cortical astrocytes.

Metabotropic glutamate receptors (mGluRs) belong to the class of G protein-coupled receptors and consist of eight different subtypes. We have characterized the structural organization of the mouse mGluR3 gene by genomic cloning in combination with rapid amplification of 5'- and 3'-cDNA ends and examined regulatory expression of mGluR3 mRNA in cultured cortical astrocytes. The mGluR3 gene consists of six exons and spans over 95 kb. Exon 1 and its preceding putative promoter are located distantly from the following protein-coding region. In the mGluR family, mGluR3 and mGluR5 are both expressed in neuronal and glial cells and are upregulated during the early postnatal period. They are, however, coupled to two distinct signaling cascades and have been shown to exert opposite influences on some functions of cultured astrocytes. In cultured astrocytes, mGluR3 and mGluR5 mRNA levels were significantly increased by exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or transforming growth factor-alpha; and EGF was more efficacious than bFGF in producing this increase. Hence, mGluR3 and mGluR5 mRNAs are concertedly upregulated in cultured astrocytes by specific growth factors. This finding suggests that the two mGluR subtypes may play an important role in maintaining the proper balance of astrocyte functions via two distinct signal transduction mechanisms.