2015 Fiscal Year Annual Research Report
| Project Area | Brain Environment |
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| Project/Area Number |
23111005
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
内匠 透 国立研究開発法人理化学研究所, 脳科学総合研究センター, シニアチームリーダー (00222092)
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| Project Period (FY) |
2011-04-01 – 2016-03-31
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| Keywords | RNA結合タンパク質 / 筋萎縮性側索硬化症 / 細胞骨格 |
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| Outline of Annual Research Achievements |
Translocated in liposarcoma/Fused in sarcoma (TLS/FUS) is an RNA-binding protein that regulates the splicing pattern of mRNA transcripts and is known to cause a type of familial amyotrophic lateral sclerosis (ALS). In the absence of TLS, Mammalian enabled (Mena), an actin-regulatory protein and a target of TLS, undergoes preferential alternative splicing. Here, we show that the ablation of TLS dysregulates the subcellular location and functions of Mena. When TLS knockout mouse embryonic fibroblasts (MEFs) were transfected with wild type Mena, it no longer accumulated at focal adhesions and peripheral structures, whereas the localization of the alternatively spliced form was maintained. Additionally, Mena’s ability to suppress the motility of cells was lost in TLS knockout MEFs. Moreover, Mena failed to promote neurite outgrowth in TLS knockout primary neurons. Taken together, TLS is intimately involved in the local cytoskeletal dynamics surrounding Mena in both fibroblasts and neurons. The robust change in cytoskeletal dynamics, as evidenced by the dysregulation of Mena in TLS knockout cells, provides a new insight into the pathogenesis of certain types of ALS.
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| Research Progress Status |
27年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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Research Products
(33 results)
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[Journal Article] Translocated in liposarcoma regulates the ditrubution and funciton of mammalian enabled, a modulator of actin dynamics2016
Author(s)
Sugiura T, Matsuda S, Kurosaka S, Nakai N, Fukumoto K, Takahashi T, Maruyama H, Imaizumi K, Matsumoto M, Takumi T
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Journal Title
FEBS J
Volume: 283
Pages: 1475-1487
DOI
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Role for neonatal D-serine signaling: prevention of physiological and bahavioral deficits in adult Pick1 knockout mice2016
Author(s)
Nomura J, Jaaro-Peled H, Lewis E, Nunez-Abades P, Huppe-Gourgues F, Cash-Padgett T, Emiliani F, Kondo MA, Furuya A, Landek-Salgado MA, Ayhan Y, Kamiya A, Takumi T, Huganir R, Pletnikov M, O'Donnell P, Sawa A
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Journal Title
Mol Psychiatry
Volume: 21
Pages: 386-393
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] FUS/TLS deficiency causes beahvioral and pathological abnormalities distinct from amyotrophic lateral sclerosis2015
Author(s)
Kino Y, Washizu C, Kurosawa M, Yamada M, Miyazaki H, Akagi T, Hashikawa T, Doi H, Takumi T, Hicks GG, Hattori N, Shimogori T, Nukina N
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Journal Title
Acta Neuropathol Commun
Volume: 3
Pages: 24
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] MOdel mice for 15q11-13 duplication syndrome exhibit late-onset obesity and altered lipid metabolism2015
Author(s)
Kishimoto R, Tamada K, Liu X, Okubo H, Ise S, Ohta H, Ruf S, Nakatani J, Kohno N, Spitz F, Takumi T
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Journal Title
Hum Mol Genet
Volume: 24
Pages: 4559-4572
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Cerebllar associative sensory learning defects in five mouse autism models2015
Author(s)
Kloth AD, Badura A, Li A, Cherskov A, Connolly SG, Giovannucci A, Bangash MA, Grasselli G, Penagarikano O, Piochon C, Tsai PT, Geschwind DH, Hansel C, Sahin M, Takumi T, Worley PF, Wang SS
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Journal Title
Elife
Volume: 9
Pages: e06085
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Transcriptome profiling of white adipose tissue in a mouse model for 15q duplication syndrome2015
Author(s)
Liu X, Tamada K, Kishimoto R, Okubo H, Ise S, Ohta H, Ruf S, Nakatani J, Kohno N, Spitz F, Takumi T
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Journal Title
Genom Data
Volume: 5
Pages: 394-396
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] FUS-regulated microRNAs in FUS Proteinopathy2015
Author(s)
Warren McGee, Jianwen Deng, Yonggui Fu, Haipeng Cheng, Kazuo Fushimi, Xiaoping Chen, Satoshi Kurosaka, Toru Takumi, Anlong Xu, Jane Y. Wu
Organizer
Neuroscience 2015
Place of Presentation
Chicago, IL, USA
Year and Date
2015-10-17 – 2015-10-21
Int'l Joint Research
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[Presentation] 発達期におけるD-セリンの役割：Pick1ノックアウトマウスをモデルとして2015
Author(s)
野村淳、H. Jaaro-Peled, E. Lewis, P. Nunez-Abades, F. Huppe-Gourgues, Tyler Cash-Padgett, F. Emiliani, M. A. Kondo, 古屋亜佐子, M. A. Landek-Salgado, Y. Ayhan, 神谷篤, 内匠透, R. Huganir, M. Pletnikov, P. O’Donnell, 澤明
Organizer
第４５回日本神経精神薬理学会、第３７回日本生物学的精神医学会
Place of Presentation
東京
Year and Date
2015-09-24 – 2015-09-26
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[Presentation] Modeling Autism2015
Author(s)
Toru Takumi
Organizer
ISN Satellite Meeting 20015, The Frontiers in Neurodevelopmental Disorders (FiND)
Place of Presentation
Sydney, Australia
Year and Date
2015-08-21
Int'l Joint Research / Invited
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[Presentation] Phase organization of clock neurons and its implications for mood disorders2015
Author(s)
Forger DB, Myung, J, Belle MDC, Cochran A, DeWoskin D, Joshi A, Stinchcombe A, Walch OJ, Takumi T, Piggins H
Organizer
XIV European Biological Rhythms Society (EBRS) and IV World Congress of Chronobiology (WCC)
Place of Presentation
Manchester, UK
Year and Date
2015-08-02 – 2015-08-06
Int'l Joint Research / Invited
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