| Project/Area Number |
24590087
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 糖転移酵素 / フコース / 膜タンパク質 / AMPA 受容体 / Fut8 / α1,6 フコース / 糖鎖 / 神経疾患ス / モデルマウ / 神経疾患 / モデルマウス |
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| Outline of Final Research Achievements |
We previously reported thatα1,6-fucosyltransferase (Fut8) knockout (Fut8-/-) mice showed a schizophrenia-like phenotype and a decrease in working memory. To understand the underlying molecular mechanism, we analyzed early-form long-term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8-/- mice. The expression levels of AMPARs in the postsynaptic density were enhanced in Fut8-/- mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which might increase sensitivity for postsynaptic depolarization, and persistently activate N-methyl-D-aspartate receptors as well as Ca2+ influx and CaMKII, and then impair LTP.
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