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1995 Fiscal Year Final Research Report Summary

Changes in cytoskeletal organization and metabolism related to maturation and aging of the neuron.

Research Project

Project/Area Number 06454697
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University

Principal Investigator

TASHIRO Tomoko  Gunma University, School of Medicine, 医学部, 助教授 (50114541)

Co-Investigator(Kenkyū-buntansha) SEKIMOTO Sumito  Gunma University, School of Medicine, 医学部, 助手 (70226661)
Project Period (FY) 1994 – 1995
Keywordscytoskeleton / axonal transport / microtubule / tubulin / neurofilament / tau protein / neurite formation / beta, beta'-iminodipropionitrile
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.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Tashiro T., Imai R., & Komiya Y.: "Early effects of β, β'-iminodipropionitrile on tubulin solubility and neurofilament phosphory; ation in the axon." J. Neurochem.63. 291-300 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sun X., Tashiro T., Hirai S., et al.: "Preparation of tau from the peripheral nerve: presence of insoluble low molecular weight tau with high phosphorylation." Biochem. Biophys. Res. Comm.210. 338-344 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sekimoto S., Tashiro T. & Komiya Y.: "Two stages in neurite formation distinguished by differences in tubulin metabolism." J. Neurochem.64. 354-363 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tashiro T., Sekimoto S., Komiya Y. et al.: "Microtubule stabilization during neurite formation: direct observation and characterization of stable microtubules." J. Cell Sci.(in pre). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tashiro, T., Imai, R.& Komiya, Y.: "Early effects of beta, beta'-iminodipropionitrile on tubulin solubility and neurofilament phosphorylation in the axon." J.Neurochem.63. 291-300 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sun, X., Tashiro, T., Hirai, S., Yamamoto, H., Miyamoto, E.& Komiya, Y.: "Preparation of tau from the peripheral nerve : presence of insoluble low molecular weight tau with high phosphorylation." Biochem.Biophys.Rea.Comm.210. 338-344 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sekimoto, S., Tashiro, T.& Komiya, Y.: "Two stages in neurite formation distinguished by differences in tubulin metabolism." J.Neurochem.64. 354-363 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tashiro, T., Sekimoto, S., Komiya, Y., Kurachi, M.& Tashiro, T.: "Microtubule stabilization during neurite formation : direct observation and characterization of stable microtubules." J.CeLL Sci.(in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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