2006 Fiscal Year Final Research Report Summary
DYNAMIC REGULATION OF THE MAINTENANCE AND FUNCTION OF NEURAL CELLS BY THE UBIOUITIN SYSTEM
| Project/Area Number |
16300126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Institute of Neuroscience, National Center of Neurology and Psychiatry |
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Principal Investigator |
WADA Keiji National Institute of Neuroscience, Department of Degenerative Neurological Diseases, Director, 神経研究所疾病研究第四部, 部長 (70250222)
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| Project Period (FY) |
2004 – 2006
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| Keywords | ubiquitin / deubiquitinating enzyme / mouse / protein degradation / neuron / neurotransmission / neuroregeneration / synapse |
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| Research Abstract |
We previously identified that ubiquitin C-terminal hydrolase Ll (UCH-L1) is the responsible gene product for the gracile axonal dystrophy (gad) phenotype (Nature Genetics, 1999). UCH-L1 is a member of the deubiquitinating enzyme family and is selectively expressed in neurons. The gad mouse that lacks the expression of UCH-L1 is pathologically characterized by dying-back type of axonal degeneration. In this study, we aimed to elucidate the mechanism of a possible dynamic regulation of the maintenance and function of neural cells by deubiquitinating enzymes. We initially showed that UCH-L1 unexpectedly binds to and stabilizes monoubiquitin in neurons. This novel activity of UCH-L1 is independent on its hydrolase activity. We subsequently identified that this novel activity of UCH-Li is involved in the regulation of the activity of P2X type of ATP receptors and the morphology of neural progenitor cells. We further identified that UCH-L3, a related molecule to UCH-L1, is involved in cell apoptosis. In the retina of UCH-L3-deficient mice, caspase-independent apoptosis increased when retinal cells were insulted. UCH-L3 may have an opposing role against UCH-L1 in the cell apoptosis. In summary, we indicate that deubiquitinating enzymes may exert their biological activities in multiple ways
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Research Products
(36 results)
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[Journal Article] Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease-associated UCH-L1 193M mutant.2007
Author(s)
Setsuie R., Wang Y.L., Mochizuki H., Osaka H., Hayakawa H., Ichihara N., Li H., Furuta A., Sano Y., Sun Y.J., Kowan J., Kabuta T., Yoshimi K., Aoki S., Mizuno Y., Noda M., Wada K.
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Journal Title
Neurochem. Int. 50
Pages: 119-129
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of multimetric variants of ubiquitin carboxyl-terminal hydrolase Ll in water by small-angle neutron scattering.2006
Author(s)
Naito S., Mochizuki H., Yasuda T., Mizuno Y., Furusaka M., Ikeda S., Adachi T., Shimizu HM., Suzuki J., Fujiwara S., Okada T., Nishikawa K., Aoki S., Wada K.
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Journal Title
Biochem Biophys Res Commun. 339
Pages: 717-725
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ubiquitin C-terminal hydrolase Ll regulates the morphology of neural progenitor cells and modulates their differentiation.2006
Author(s)
Sakurai M., Ayukawa K., Setsuie R., Nishikawa K., Hara Y., Ohashi H., Nishimoto M., Abe T., Kudo Y., Sekiguch M., Sato Y, Aoki S., Noda M., Wada K.
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Journal Title
J. Cell Sci. 119(Pt1)
Pages: 162-171
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells.2006
Author(s)
Sato A., Arimura Y., Manago Y., Nishikawa K., Aoki K., Wada E., Suzuki Y., Osaka H., Setsuie R., Sakurai M., Amano T., Aoki S., Wada K., Noda M.
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Journal Title
J. Cell. Physiol. 209
Pages: 172-182
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Localization of ubiquitin C-terminal hydrolase LI in mouse ova and its function in the plasma membrane to block polyspermy.2006
Author(s)
Sekiguchi S., Kwon J., Yoshida E., Hamasaki H., Ichinose S., Hideshima M., Kuraoka M., Takahashi A., Ishii Y., Kyuwa S., Wada K., Yoshikawa Y.
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Journal Title
Am. J. Pathol. 169
Pages: 1722-1729
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice.2005
Author(s)
Mi W., Beirowski B., Gillingwater T.H., Adalbert R., Wagner D., Grumme D., Osaka H., Conforti L., Arnhold S., Addicks K., Wada K., Ribchester R.R., Coleman M.P.
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Journal Title
Brain. 128
Pages: 405-416
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase Ll.2005
Author(s)
Manago Y., Kanahori Y., Shimada A., Sato A., Amano T., Sato Y., Setsuie R., Sakurai M., Aoki S., Wang Y.L., Osaka H., Wada K., Noda M.
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Journal Title
J. Neurochem. 92
Pages: 1061-1072
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Developmental regulation of ubiquitin C-terminal hydrolase isozyme expression during spermatogenesis in mice.2004
Author(s)
Kwon J., Wang Y.L., Setsuie R., Sekiguchi S., Sakurai M., Sato Y., Lee W.W., Ishii Y., Kyuwa S., Noda M., Wada K., Yoshikawa Y.
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Journal Title
Biol. Reprod. 71
Pages: 515-521
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Accumulation of beta-and gamma-synucleins in the ubiquitin C-terminal hydrolase L1 deficient gad mouse.2004
Author(s)
Wang Y.L., Takeda A., Osaka H., Hara Y., Furuta A., Setsuie R., Sun Y.J., Kwon J., Sato Y., Sakurai M., Noda M., Yoshikawa Y., Wada K.
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Journal Title
Brain Res 1019
Pages: 1-9
Description
「研究成果報告書概要(欧文)」より
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