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.

Metabotropic glutamate receptor in C. elegans.

Takeshi Ishihara , Isao Katsura

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.