PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis

PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis
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DOI:
10.1016/j.cub.2005.06.059
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发表时间:
2005-08-09
期刊:
影响因子:
9.2
通讯作者:
Cantley, LC
Cantley, LC
中科院分区:
生物学1区
文献类型:
--
作者:
Field, SJ;Madson, N;Cantley, LC

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肌醇磷脂在调节细胞骨架和囊泡运输方面发挥着重要作用,这些都是卵裂沟中潜在的重要过程。然而,目前还不清楚哪种磷脂酰肌醇在胞质分裂过程中发挥作用。一项系统的分析,以确定在卵裂沟是否可能存在任何磷脂酰肌醇或是否具有重要的功能,尚未发表。几项研究提示,一个或多个磷脂酰肌醇可能在卵裂沟起作用。其中最好的是识别干扰胞质分裂的磷脂酰肌醇修饰酶突变的遗传数据(Ptdlns(4)Ptdlns(4)P-5-激酶在S.pombe[1,2]和PI-4-Kinase在D.Blackogaster中[3])。这些实验的遗传性质使得它们对细胞质分裂的贡献可能有多直接留下了疑问。在这里,我们证明了单一的磷脂酰肌醇,PtdIns(4,5)P2,特异性地积累在沟槽上。与PtdIns(4,5)P2的干扰干扰了质膜与沟槽处收缩环的粘连。最后,四种不同的干预Ptdlns(4,5)P2的不同干预措施都会损害细胞质分裂。我们得出结论,PtdIns(4,5)P2存在于卵裂沟中,是正常胞质分裂所必需的,至少部分是因为PtdIns(4,5)P2在收缩环和质膜之间的粘连中发挥了作用。
Phosphoinositides play important roles in regulating the cytoskeleton and vesicle trafficking, potentially important processes at the cleavage furrow. However, it remains unclear which, if any, of the phosphoinositides play a role during cytokinesis. A systematic analysis to determine if any of the phosphoinositides might be present or of functional importance at the cleavage furrow has not been published. Several studies hint at a possible role for one or more phosphoinositides at the cleavage furrow. The best of these are genetic data identifying mutations in phosphoinositide-modifying enzymes (a Ptdlns(4)P-5-kinase in S. pombe [1, 2] and a PI-4-kinase in D. melanogaster [3]) that interfere with cytokinesis. The genetic nature of these experiments leaves questions as to how direct may be their contribution to cytokinesis. Here we show that a single phosphoinositide, PtdIns(4,5)P2, specifically accumulates at the furrow. Interference with PtdIns(4,5)P2 interferes with adhesion of the plasma membrane to the contractile ring at the furrow. Finally, four distinct interventions to specifically interfere with Ptdlns(4,5)P2 each impair cytokinesis. We conclude that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal cytokinesis at least in part because of a role in adhesion between the contractile ring and the plasma membrane.