Metabotropic glutamate receptors 5 (mGluR5) are members of the growing group C G protein-coupled receptor family. Widely expressed in mammalian brain, they are involved in modulation of the glutamate transmission. By means of transfection of mGluR5 receptors in COS-7 cells and primary hippocampal neurons in culture followed by immunocytochemistry and quantitative image analysis and by a biochemical assay, we have studied the internalization of mGluR5 splice variants. mGluR5a and -5b were endocytosed in COS-7 cells as well as in axons and dendrites of cultured neurons. Endocytosis occurred even in the absence of receptor activity, because receptors mutated in the glutamate binding site were still internalized as well as receptors in which endogenous activity had been inhibited by an inverse agonist. We have measured a constitutive rate of endocytosis of 11.7%/min for mGluR5a. We report for the first time the endocytosis pathway of mGluR5. Internalization of mGluR5 is not mediated by clathrin-coated pits. Indeed, inhibition of this pathway by Eps15 dominant negative mutants did not disturb their endocytosis. However, the large GTPase dynamin 2 is implicated in the endocytosis of mGluR5 in COS-7. mGluR5 is the first shown member of the group C G-protein coupled receptor family internalized by a nonconventional pathway.Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. It exerts its effects by binding to ionotropic and metabotropic receptors. Metabotropic glutamate receptors (mGluRs) 1 belong to the seven-transmembrane domain G protein-coupled receptor (GPCR) family. Together with calcium-sensing receptors, ␥-aminobutyric acid receptor B (GABA B ) and pheromone, olfactory and taste receptors, mGluRs form the third family of GPCRs (group C) (for reviews, see Refs. 1 and 2). They have little homology with other GPCRs from groups A and B and are characterized by a large N-terminal extracellular domain that binds glutamate. Eight genes code for mGluRs that generate more than 15 proteins by alternative splicing. On the basis of their sequence similarity, pharmacology, and signal transduction mechanisms, mGluRs have been classified into three groups. Group 1 consists of mGluR1 and mGluR5 that are preferentially positively coupled to phospholipase C via G q/11 proteins. mGluRs of group 2 and 3 are negatively coupled to adenylate cyclase. Group 1 mGluRs are expressed in neuronal and glial cells within the brain, and receptor activation has been implicated in several forms of synaptic plasticity.Currently, very little is known about the targeting and trafficking mechanisms of mGluRs in cells. During the last few years, attention has focused mainly on endocytosis of a subtype of ionotropic glutamate receptors: the ␣-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors. Internalization of AMPA receptors in response to various stimuli is an important process for the rapid attenuation of neurotransmission during synaptic plasticity (3). By different approaches, it has been s...

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The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which plays a key role in isoprenoid biosynthesis, catalyses the synthesis of mevalonate from HMG-CoA. Insects do not synthesize cholesterol de novo, rather mevalonate derivatives lead to non-sterol isoprenoids which are essential for development and reproduction. In this paper, we describe an HMG-CoA reductase of the moth Agrotis ipsilon and we report its expression in fat body, ovary, muscle, brain and corpora allata tissues of adult specimens. The analysis of the cDNA reveals that it encodes a polypeptide of 833 amino acids (Mr = 89785). Alignments of this HMG-CoA reductase from A. ipsilon with the homologous sequences of other eukaryotes shows a high degree of conservation in all species studied. Parsimony analysis based on these alignments produced dendrograms congruent with the current systematic schemes. This suggests that, during eukaryote evolution, HMG-CoA reductase diversified in parallel with taxonomic splitting.

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