Multinuclear giant cell formation mechanism of Krabbe disease patient brain

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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 PsychosinePsychosine 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 yeastPsychosine 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.