Project/Area Number |
10102006
|
Research Category |
Grant-in-Aid for Specially Promoted Research
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | RIKEN (2002) Kyoto University (1998-2001) |
Principal Investigator |
TAKEICHI Masatoshi RIKEN Center for Developmental Biology, Group Director, 高次構造形成研究グループ, グループディレクター (00025454)
|
Co-Investigator(Kenkyū-buntansha) |
UEMURA Tadashi Kyoto University, Faculty of Science, Associate Professor, 理学研究科, 助手 (80213396)
CHISAKA Osamu Kyoto University, Faculty of Science, Associate Professor, 理学研究科, 助教授 (80188474)
|
Project Period (FY) |
1998 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥361,200,000 (Direct Cost: ¥321,000,000、Indirect Cost: ¥40,200,000)
Fiscal Year 2002: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Fiscal Year 2001: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Fiscal Year 2000: ¥47,000,000 (Direct Cost: ¥47,000,000)
Fiscal Year 1999: ¥60,000,000 (Direct Cost: ¥60,000,000)
Fiscal Year 1998: ¥80,000,000 (Direct Cost: ¥80,000,000)
|
Keywords | cadherin / catenin / synapse / neuron / hippocampus / cell adhesion / cerebellum / Purkinje cell / 神経回路 / プルチンエ細胞 / シナプシン / PSD-95 / 網膜 / 脳 / LTP / p120 |
Research Abstract |
1. We have shown that under the suppression of cadherin function, dendritic spines abnormally elongate, axon-spine contacts are destabilized, and presynaptic vesicle accumulation and postsynaptic density protein organization are impaired. These findings provide the first compelling evidence for the important role of cadherin in synapse formation and maintenance 2. We analyzed hippocampal neurons collected from αN-catenin mutant mice, and found that their dendritic spines abnormally elongated, genetically confirming the above in vitro results. We also found that, in the cerebellum of αN-catenin knockout mice, Purkinje cell migration is partly blocked, suggesting that this catenin is also important for the migration of particular subsets of neuronal precursors. 3. Cadherin-11 knockout mice showed aberrant emotional behavior, such as reduced anxiety, suggesting that this cadherin is involved in the regulation of physiological brain functions. Cadherin-8 knockout mice show another behavioral phenotypes, which are under detailed investigation. 4. We found that p120-catenin has the activity to bind cytoplasmic microtubules, suggesting that p120-catenin functions as a linker between microtubules and cell-cell junctions, controlling microtubule networks. This is the first demonstration for the interactions of the cadherin and microtubule systems. 5. We discovered that the seven-passed transmembrane cadherin Flamingo plays a role in the regulation of planer cellular polarity. 6. We identified a unique cadherin, present in both vertebrates and invertebrates, and in the former, it is specifically expressed in the outerplexiform layer of retina.
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