Inhibition of cytokinesis by a lipid metabolite, psychosine

Although a number of cellular components of cytokinesis have been identifie d, little is known about the derailed mechanisms underlying this process. H ere, 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 cytok inesis, 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 contrac tile movement was detected in which the cellular contents of one of the hem ispheres of the contracting cell were transferred into its counterpart. Fin ally, the cleavage furrow disappeared and cytokinesis was reversed. Psychos ine treatment also induced giant clots of actin filaments in the cells that probably consisted of small vacuoles with filamentous structures, suggesti ng that psychosine affected actin reorganization, These observations could account for the formation of multinuclear globoid cells in the brains of pa tients with globoid eel leukodystrophy, a neurological disorder characteriz ed by the accumulation of psychosine due to galactosylceramidase deficiency .