Inhibition of cytokinesis by a lipid metabolite, psychosine.
Inhibition of cytokinesis by a lipid metabolite, psychosine.
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DOI：
10.1083/jcb.149.4.943
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发表时间：
2000-05-15
期刊：
影响因子：
--
通讯作者：
Kozutsumi Y
中科院分区：
文献类型：
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作者：
Kanazawa T;Nakamura S;Momoi M;Yamaji T;Takematsu H;Yano H;Sabe H;Yamamoto A;Kawasaki T;Kozutsumi Y
尽管胞质分裂的许多细胞成分已被鉴定，但对该过程背后的详细机制知之甚少。在这里，我们报道了源自半乳糖神经酰胺的脂质代谢物精神氨酸（半乳糖基鞘氨醇），由于抑制胞质分裂而诱导多种非贴壁和贴壁细胞形成多核细胞。当将精神氨酸添加到人类骨髓单核细胞系U937（这是测试的细胞系中最敏感的细胞系）时，分裂沟要么不完全要么几乎完全形成。然而，检测到异常的收缩运动，其中收缩细胞的一个半球的细胞内容物被转移到其对应部分。最后，卵裂沟消失，胞质分裂逆转。赛西林治疗还在细胞中诱导了巨大的肌动蛋白丝凝块，这些凝块可能由具有丝状结构的小液泡组成，这表明赛西林影响了肌动蛋白重组。这些观察结果可以解释球状细胞脑白质营养不良患者大脑中多核球状细胞的形成，球状细胞脑白质营养不良是一种神经系统疾病，其特征是由于半乳糖神经酰胺酶缺乏而导致精神分裂症积聚。
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.