2005 Fiscal Year Final Research Report Summary
Molecular characterizations of the Drosophila homolog of the fragile X gene FMR1 in neuronal morphology and function
| Project/Area Number |
15207002
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genetics/Genome dynamics
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SIOMI Haruhiko The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60202107)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOE Minoru Tokyo Metropolitan Institute for Neuroscience, Group leader, 東京都神経科学総合研究所, 主任研究員 (50261839)
ISHIDA Norio National Institute of Advanced Industrial Science and Technology, Institute for Biological Resources and Functions, Group leader, 生物機能工学研究部門, グループ長 (00344234)
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| Project Period (FY) |
2003 – 2005
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| Keywords | fragile X syndrome / FMR1 / Drosophila / olfactory learning and memory / neuro-muscular junction (NMJ) / circadian rhythms / RNAi |
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| Research Abstract |
Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a translational repressor. Our previous work on the Drosophila homolog of FMR1 gene, dFMR1,showed that dFMR1 interacts with RNAi-related molecules, such as AGO2 and small RNA (Ishizuka et al.2002). Recently we showed that dFMR1-associated complexes also contain a courtship regulator Lingerer (Lig). Consistently, dFMR1 and Lig are co-expressed in the nervous system. We found that Lig hypomorphs display shrunken synaptic terminals at the neuromuscular junction in third instar larvae, whereas in dFMR1 mutant synaptic terminals were expanded. Genetic interaction between the two genes was implicated because dFMR1/Lig double mutants restore normal synaptic structure.
We also demonstrated that dFMR1 flies exhibit defects in olfactory memory. Short-term memory, but not long-term memory, is impaired in dFMR1 flies. In addition, we were able to show that the observed deficits in circadian locomotor activity in dFMR1 flies can be rescued by an introduction of the human FMR1 gene as a trans gene.
Further characterization of dFMR1-Lingerer-AGO2 interaction should help us to understand translational regulation by dFMR1 and thereby the molecular mechanisms that cause the fragile X syndrome.
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