| Project/Area Number |
06454697
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
TASHIRO Tomoko Gunma University, School of Medicine, 医学部, 助教授 (50114541)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIMOTO Sumito Gunma University, School of Medicine, 医学部, 助手 (70226661)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | cytoskeleton / axonal transport / microtubule / tubulin / neurofilament / tau protein / neurite formation / beta, beta'-iminodipropionitrile / 加齢変化 / チューブリン / 培養神経細胞 / 坐骨神経 / axonal transport / β,β'-iminodipropionitrile / tubulin / neurofilament protein / tau protein / dorsal root ganglion cell / neurite formation |
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| Research Abstract |
To understand the changes in cytoskeletal organization and metabolism which underly neurodegenerative processes observed during normal aging as well as disease, we studied the properties of the axonal cytoskeleton in cultured neurons and in vivo using the axonal transport system.
One of the major characteristics of the axonal cytoskeleton is the presence of a large amount of tubulin which is insoluble under various conditions to depolymerize cytoplasmic microtubules (MTs). The proportion of such insoluble tubulin varies during development or regeneration, suggesting its involvement in MT stabilization in the axon. In dorsal root ganglion neurons in culture, we found that insoluble tubulin appeared and increased in amount during neurite formation. Using video-enhanced microscopy, insoluble tubulin was further identified with MTs which were stable even after exposure to extracellular medium by detergent demembranation.
Phosphorylation state of neurofilaments (NFs) was found to be one of the factors regulating tubulin solubility through NF-MT interaction by the use of beta, beta'-iminodipropionitrile which disrupts the organization of the axonal cytoskeleton and inhibits NF transport.
MT-associated proten tau was studied as another factor in MT stabilization. Compared with tau associated with brain MTs, which consists of many isoforms ranging between 44-66kDa and wide pI ranges, tau isolated from the peripheral axon contained only the most acidic isofoms that were highly phosphorylated. More than 60% of axonal tau was insoluble. Axonal transport studies in the sciatic nerve showed that insoluble tau was transported with insoluble tubulin at the slowest rate in SCa, suggesting the close association between tau and the stable MTs. Soluble tau was transported significantly faster in SCb.
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