| Project/Area Number |
18500250
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
HIRATA Tatsumi National Institute of Genetics, Department of Integrated Genetics, Associate Professor (80260587)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | M6a / Axon outgrowth / Knockout mouse / Neural development / 軸策ガイダンス / プロテオリピッド |
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| Research Abstract |
During development, axons vigorously elongate, still carefully controlling the speed, to connect with the targets. It is generally believed that inhibition of axon growth is achieved by growth cone collapse involving disruption of the actin-based tip by repulsive guidance molecules. In the natural environment, however, axons pause or reduce the speed of elongation while maintaining well-organized cytoskeletons. We found that axon growth is inhibited without destroying the actin-based structure or motility when antibodies bind to four-transmembrane protein M6a. Surprisingly, M6a-deficient axons isolated from M6a knockout mice can grow actively but fail to pause in response to the antibodies, indicating the gain-of-function property of the antibody action. M6a selectively translocates to membrane edges independently of the cytoskeletons and deforms the cell membrane into outward tubules. Disturbance of the proper localization on the growth cone edge membrane is suggested to underlie the axon-outgrowth inhibition induced by the antibodies. All major axon tracts were established in the M6a knockout mice. Detailed analyses of M6a knockout mice will reveal subtle phenotypes and clarify the physiological function of M6a.
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