title: In developing Drosophila neurones the production of gamma-amino butyric acid is tightly regulated downstream of glutamate decarboxylase translation and can be influenced by calcium.
abstract: The presented work pioneers the embryonic Drosophila CNS for studies of the developmental regulation and function of gamma-amino butyric acid (GABA). We describe for the first time the developmental pattern of GABA in Drosophila and address underlying regulatory mechanisms. Surprisingly, and in contrast to vertebrates, detectable levels of GABA occur late during Drosophila neurogenesis, after essential neuronal proliferation and growth have taken place and synaptogenesis has been initiated. This timeline is almost unchanged when the GABA synthetase glutamate decarboxylase (GAD) is strongly misexpressed throughout the nervous system suggesting a tight post-translational regulation of GABA expression. We confirmed such GABA control mechanisms in an independent model system, i.e. primary Drosophila cell cultures raised in elevated [K+]. The data suggest that, in both systems, GABA suppression occurs via control of GAD activity. Using developing embryos and cell cultures as parallel assay systems for pharmacological and genetic studies we show that the negative regulation of GAD can be overridden by drugs known to elevate intracellular free [Ca2+]. Our results provide the basis for investigations of genetic mechanisms underlying the observed phenomenon, and we discuss the potential implications of this work for Drosophila neurogenesis but also for a general understanding of GAD regulation.
authors.affiliation: Institute of Genetics, University of Mainz, J.-J.-Becherweg 32, D-55128 Mainz, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Küppers
authors.forename: Natalia
authors.initials: N
authors.lastname: Sánchez-Soriano
authors.forename: Johannes
authors.initials: J
authors.lastname: Letzkus
authors.forename: Gerhard M
authors.initials: GM
authors.lastname: Technau
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004331:Drosophila melanogaster; D004625:Embryo, Nonmammalian / Q000294:innervation; D018507:Gene Expression Regulation, Developmental; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D011188:Potassium; D002118:Calcium