Worm Breeder's Gazette 14(3): 40 (June 1, 1996)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
DNA Research Center, National Institute of Genetics, Mishima, 411 Japan
Metabotropic glutamate receptors (mGluRs) are a class of glutamate receptors that contain seven transmembrane domains and that are coupled with G-proteins. In mammals, eight mGluR genes are identified, and those receptor subtypes are divided into three groups according to homology, pharmacology, and downstream signal transduction system. The receptors belonging to one of the groups (mGluR1 and mGluR5) are coupled to IP3/Ca2+ signal transduction systems, while the other six receptors are involved in the inhibition of cAMP formation. The latter are subdivided further into two groups by the response to agonists. By studying knockout mice lacking mGluR genes, mGluRs are shown to be involved in higher order functions in the mammalian brain. Mice lacking mGluR1 gene are deficient in associative learning dependent on hippocampus and cerebellum, in accordance with reduced long-term potentiation in hippocampal CA1 region and with deficit of the cerebellar long-term depression, respectively. Mice lacking mGluR5 gene show deficiency in ON response in visual transmission, while they show normal OFF response. Recently, it was found that mice lacking mGluR1 gene show abnormal neuronal network formation in cerebellum. In C. elegans genome project, a mGluR gene (ZC506.4) has been identified. According to the amino acid sequence homology to mammalian mGluRs, it belongs to the Gi-coupled mGluR groups, but it is difficult to classify it further. To investigate the expression pattern of the C. elegans mGluR gene, we generated transgenic worms carrying a chimeric mGluR-GFP fusion gene, which contains most of the mGluR coding region, under the control of the mGluR gene promoter. The fusion gene is expressed in several kinds of interneurons and motorneurons including RMD, AIA and PVQ. It is also expressed in pharyngeal interneurons. We also examined the expression of the GFP gene that is transcriptionally fused to the 5' regulatory region of the mGluR gene. Its expression seems essentially the same as that of the chimeric gene. To elucidate the functions of the mGluR in C. elegans, we isolated a mutant of the mGluR gene by insertion and imprecise excision of Tc1. The mutation deletes a 1.8kb fragment within the gene that encodes about 300 amino acids of the first extracellular domain. The mutant grows normally but shows a Loopy phenotype. Since laser ablation of the RMD neurons in a wild type animal causes the Loopy phenotype (Elkes and Kaplan, WBG 12 (5) : 66), the expression of the mGluR in RMD neurons may be responsible for normal head movement. We also examined other behaviors including chemotaxis , adaptation, and osmotic avoidance. However, as far as we tested, all of them are normal except that thermotaxis seems to be slightly affected. We will further examine behavioral assays to find function of the mGluR gene in interneurons.