Multinuclear giant cell formation mechanism of Krabbe disease patient brain

• Project/Area Number: 13470488
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: KOZUTSUMI Yasunori Kyoto University, Graduate school of Biostudies, Professor, 生命科学研究科, 教授 (70205425)
• Project Period (FY): 2001 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥13,700,000 (Direct Cost: ¥13,700,000); Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000); Fiscal Year 2001: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: krabbe disease / Globoid cell / multinuclear cell / psychosine / tryptophan / yeast / organelle / sphingolipid / Krabbe病 / アクチン / GIoboid cells / TDAG8 / multicopy library

Research Abstract

The goal of this project is to understand the mechanism underlining multinuclear cell formation by psychosine. The following findings were obtained during 3years.
(1) Multinuclear giant cell formation mechanism by Psychosine
Psychosine inhibited cytokinesis and induced multinuclear cells by disrupting membrane transport to the cleavage furrow during cytokinesis.
(2) Abnormal distribution of intracellular organelles by psychosine.
Psychosine induced selective dispersal of lysosomes and earl endosomes without affecting the endocytosis activity of the cells.
(3) Genes involved in resistance to psychosine in yeast
Psychosine resistant genes were isolated using yeast system. One of genes encodes tryptophan permease. Tryptophan permease was degraded by the treatment of psychosine via the Golgi-vacuole membrane transport system.

Research Products

• [Publications] Kakio et al.: "Formation of a membrane-active form of amyloid betaprotein in raft-like model membranes"Biochem.Biophys.Res.Commun. 303(2). 514-518 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kakio et al.: "Interactions of amyloid β-protein with various gangliosides in raft-like membranes : importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid"Biochemistry. 41(23). 7385-7390 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kozutsumi et al.: "Sphingolipids involved in the induction of multinuclear cell formation"Biochim Biophys Acta. 1582(1-3). 138-143 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kasahara et al.: "Association of GPI-anchored protein TAG-1 with src-family kinase Lyn in lipid rafts of cerebellar granule cells."Neurochem Res. 27(7-8). 823-829 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamaji et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J Biochem. 129(4). 521-527 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett. 488(3). 190-195 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kakio et al.: "Formation of a membrane-active form of amyloid betaprotein in raft-like model membranes"Biochem.Biophys.Res.Commun.. 303(2). 514-518 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kakio et al.: "Interactions of amyloid E_*-protein with various gangliosides in raft-like membranes : importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid"Biochemistry. 41(23). 7385-7390 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kozutsumi et al.: "Sphingolipids involved in the induction of multi-nuclear cell formation"Biochim Biohy Acta.. 1582(1-3). 138-143 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kasahara et al.: "Association of GPI-anchored protein TAG-1 with src-family kinase Lyn in lipid rafts of cerebellar granule cells"Neurochem Res.. 27(7-8). 823-829 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamaji.et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J Biochem. 129(4). 521-527 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett.. 488(3). 190-195 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kakio et al.: "Formation of a membrane-active form of amyloid betaprotein in raft-like model membranes"Biochem.Biophys.Res.Commun.. 303(2). 515-518 (2003)
• [Publications] Kakio et al.: "Interaction between Amyloid b-Protein Aggregates and Membranes"J.Pep.Sci.. (発表予定).
• [Publications] Momoi et al.: "SLII(YGR212W)is a major gene conferring resistance to sphingolipid biosynthesis inhibitor ISP-1 and encodes an ISP-1 N-acetyltransferase in yeast"Biochemical J. (発表予定).
• [Publications] K.kasahara et al.: "Association of GPI-anchored protein TAG-1 with src-family kinase Lyn in lipid rafts of cerebellar granule cells"Neurochem Res. 27. 823-829 (2002)
• [Publications] A.Ikeda et al.: "Genonmic organization and fine-mapping of the human leucine zipper-bearing kinase (LZK) gene"J Biochem Mol Biol Biophys.. 6. 113-117 (2002)
• [Publications] Y.Kozutsumi et al.: "Sphingolipids involved in the induction of multinuclear cell formation"Biochim Biophys Acta. 1582. 138-143 (2002)
• [Publications] A.Kakio et al.: "Interactions of amyloid beta-protein with various gangliosides in raft-like membranes : importance of GM1 ganglioside-bound form"Biochemistry. 41. 7385-7390 (2002)
• [Publications] A.Kakio et al.: "Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid"J. Biol. Chem.. 276・27. 24985-24990 (2001)
• [Publications] T.Yamaji et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J. Biochem.. 129・4. 521-527 (2001)
• [Publications] A.Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett.. 488・3. 90-95 (2001)
• [Publications] A.Ikeda et al.: "Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH(2)-Terminal Kinase Pathway"J. Biochem.. 130・6. 773-781 (2001)