We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One of important biochemical consequence of DTor-RNAi expression in fly brains was up-regulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. (This work was supported bythe basic science research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2015R1D1A3A01018497)

Early onset torsion dystonia is caused by mutations in DYT1 gene in humans. Two deletion mutations and one missense mutation were found from patients with this devastating disorder. The molecular and cellular etiology underlying this disorder is not still understood yet. Because vertebrates have more than 4 homologs in their genomes, it is very hard to elucidate the exact in vivo functions of Torsin1A. Instead, Drosophila has only one homolog named Torsin. To investigate the in vivo functions of Torsin, we generated and characterized transgenic flies expressing coding regions of Torsin mRNA or double stranded inhibitory DNA constructs (RNAi). The specific antibodies for Drosophila Torsin (DTor) also were generated. The transgenic expression of DTor cDNA or RNAi in all tissue induced significant changes in DTor proteins levels. Even though expression of DTor cDNA in neuronal system increased the amount of DTor proteins, expression of DTor RNAi did not significantly altered the amount of DTor. Consistent with this result, the numbers of flies with motor-activity were not discernible among neuronal expression lines. However, flies expressing DTor cDNA or RNAi on muscles showed significantly altered locomotor ability, suggesting that DTor plays important roles in regulating motor-activity at the post-synaptic terminals of motor neurons. In addition, DTor over-expressing flies showed increased resistance to H2O2. In the future study, we will found how those phenotypes were accomplished by performing various experiments. (NRF-2012R1A1A4A01011674: HRF-S-201.-6)

Early onset torsion dystonia is caused by mutations in DYT1 gene in humans. The molecular and cellular etiology underlying this disorder is not still understood yet. Because vertebrates have more than 4 homologs in their genomes, it is very hard to elucidate the exact in vivo functions of Torsin1A. Instead, Drosophila has only one homolog named Torsin. To investigate the in vivo functions of Torsin, we generated and characterized transgenic flies expressing coding regions of Drosophial Torsin (DTor) cDNA or double stranded inhibitory DNA constructs (RNAi). The transgenic expression of DTor cDNA or RNAi in all tissue induced significant changes in DTor proteins levels as well as ability of motor controls. In addition, DTor over-expressing flies showed increased resistance to H2O2 or paraquat. In the future study, we will found how those phenotypes were accomplished by performing various experiments.