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.

中文翻译：

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果蝇肌醇1,4,5-三磷酸受体突变体改变了谷氨酸神经传递的稳态。

果蝇InsP3R基因（itpr）中的突变体是飞行缺陷的。野生型InsP3R在胺能神经元中的表达拯救了飞行。但是，InsP3R突变体的中枢神经系统中导致飞行不正常行为的分子和细胞变化仍然未知。为了了解果蝇InsP3R突变体中飞行表型的分子基础，用从成年头部和胸部分离的RNA进行了微阵列筛选。我们发现影响神经元和肌肉兴奋性的几个基因的下调。其中，进一步研究了谷氨酰胺合成酶2的作用。该酶降低突触处的谷氨酸水平。我们的研究结果表明，Gs2（谷氨酰胺合成酶2）的转录本和谷氨酸水平与InsP3R表型精确而相反，可以通过Gs2的突变等位基因进行挽救，即Gs2（m13）。通过测量InsP3R突变体的谷氨酸能突触（成人飞行神经肌肉接头）处的轴突分支和突触数量，我们得出结论，谷氨酸稳态是通过细胞非自主机制改变的，并且可能是观察到的重要基础。飞行缺陷。