Homeostasis of glutamate neurotransmission is altered in Drosophila Inositol 1,4,5-trisphosphate receptor mutants.
Mutants in the Drosophila InsP3R gene (itpr) are flight defective. Expression of the wild-type InsP3R in aminergic interneurons rescues flight. However, molecular and cellular changes in the central nervous system of InsP3R mutants that lead to flightless behavior remain unknown. To understand the molecular basis of flight phenotypes in Drosophila InsP3R mutants a microarray screen was done with RNA isolated from adult heads and thoraces. We found down-regulation of several genes that affect the excitability of neurons and muscles. Among these the role of glutamine synthetase 2 was investigated further. This enzyme reduces glutamate levels at the synapse. Our results show that Gs2 (glutamine synthetase 2) transcripts and glutamate levels correspond precisely but inversely, with InsP3R phenotypes, which can be rescued by a mutant allele for Gs2, namely, Gs2(m13). From measuring axonal branches and synapse number at a glutamatergic synapse--the adult flight neuromuscular junction--of InsP3R mutants, we conclude that glutamate homeostasis is altered through a cell non-autonomous mechanism, and is likely to be an important basis for the observed flight defects.
Nair
Shalima
S
National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore, 560065, India.
Agrawal
Neha
N
Hasan
Gaiti
G
D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004594:Electrophysiology; D015870:Gene Expression; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000294:innervation; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D029721:Drosophila Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018698:Glutamic Acid; C083818:glutamine synthetase 2; D005974:Glutamate-Ammonia Ligase