Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein.
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 important biochemical consequence of DTor-RNAi expression in fly brains was upregulation 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. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.
Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea; Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 14066, Republic of Korea.
Phuong
0000-0003-2191-6985
P
Nguyen
Korea Basic Science Institute, Seongbuk-gu, Seoul 02841, Republic of Korea.
Jong Bok
0000-0003-2058-5045
JB
Seo
Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea; Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 14066, Republic of Korea.
Hyo-Min
HM
Ahn
Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea; Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 14066, Republic of Korea.
Young Ho
YH
Koh
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007814:Larva / Q000235:genetics; D018832:Molecular Chaperones / Q000378:metabolism*; D009043:Motor Activity / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D018832:Molecular Chaperones; D058570:TOR Serine-Threonine Kinases; C108175:TOR1A protein, human; C416303:target of rapamycin protein, Drosophila