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© The Rockefeller University Press, 0021-9525/2000//943 $5.00
The Journal of Cell Biology, Volume 149, Number 4, , 2000 943-950

Original Article

Inhibition of Cytokinesis by a Lipid Metabolite, Psychosine



Takayuki Kanazawaa, Sachiko Nakamuraa, Michiko Momoib, Toshiyuki Yamajia, Hiromu Takematsub, Hajime Yanoc, Hisataka Sabec, Akitsugu Yamamotod, Toshisuke Kawasakia, and Yasunori Kozutsumib

a Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
b Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
c Department of Molecular Biology, Osaka Bioscience Institute, Suita 565-0874, Japan
d Department of Physiology and Liver Research Center, Kansai Medical University, Moriguchi 570-0074, Japan
Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan.81-75-753-460581-75-753-4562

yasu{at}pharm.kyoto-u.ac.jp

Although a number of cellular components of cytokinesis have been identified, little is known about the detailed mechanisms underlying this process. Here, we report that the lipid metabolite psychosine (galactosylsphingosine), derived from galactosylceramide, induced formation of multinuclear cells from a variety of nonadherent and adherent cells due to inhibition of cytokinesis. When psychosine was added to the human myelomonocyte cell line U937, which was the most sensitive among the cell lines tested, cleavage furrow formed either incompletely or almost completely. However, abnormal contractile movement was detected in which the cellular contents of one of the hemispheres of the contracting cell were transferred into its counterpart. Finally, the cleavage furrow disappeared and cytokinesis was reversed. Psychosine treatment also induced giant clots of actin filaments in the cells that probably consisted of small vacuoles with filamentous structures, suggesting that psychosine affected actin reorganization. These observations could account for the formation of multinuclear globoid cells in the brains of patients with globoid cell leukodystrophy, a neurological disorder characterized by the accumulation of psychosine due to galactosylceramidase deficiency.

Key Words: cytokinesis • multinuclear cell • globoid cell leukodystrophy • psychosine • actin filament

© 2000 The Rockefeller University Press

Abbreviations used in this paper: GalCer, galactosylceramide; GlcPsy, glucopsychosine; GLD, globoid cell leukodystrophy; Ia, immune response antigen; Psy, psychosine; SPC, sphingosylphosphorylcholine; TPA, 12-O-tetradecanoylphorbol acetate.


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