Role for phosphatidylinositol in nuclear envelope formation
Role for phosphatidylinositol in nuclear envelope formation
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DOI：
10.1042/0264-6021:3560495
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发表时间：
2001-06-01
影响因子：
4.1
通讯作者：
Poccia, DL
中科院分区：
文献类型：
--
作者：
Larijani, B;Barona, TM;Poccia, DL
PtdIns是一种次要的膜磷脂，在信号转导中起重要作用。最近，在肌醇环3-位上磷酸化的PtdIns的衍生物被认为与构成膜交通的调节和膜融合事件有关。核膜(NE)的组装是有丝分裂过程中的关键步骤，也可能涉及膜融合反应。因此，我们在体外研究了PtdIns和磷脂酰肌醇3-激酶(PI-3K)在NE形成中的作用。PI-3K的两种特异性抑制剂Wortmannin和LY294002可阻断GTP诱导的去甲肾上腺素的形成，提示PtdIns在3-位的磷酸化有一定的作用。PtdIns特异性磷脂酶C模拟GTP水解酶作为NE形成的诱导剂。这种诱导依赖于膜泡亚组分(MV1)，通过异核二维核磁共振光谱确定，该亚组分高度富含PtdIns。根据这些结果，我们认为MV1群体是富含PtdIns的膜的来源，可能通过产生破坏膜稳定的脂二酰甘油来促进融合。
PtdIns is a minor membrane phospholipid that is important in signal transduction. Recently, derivatives of PtdIns phosphorylated at the 3-position of the inositol ring have been implicated in the regulation of constitutive membrane traffic and in membrane fusion events. Assembly of the nuclear envelope (NE), a crucial step in the progress of mitosis, is also likely to involve membrane fusion reactions. We therefore investigated the role of PtdIns and phosphoinositide 3-kinase (PI-3K) activity in NE formation in vitro. GTP-induced NE formation was blocked by wortmannin and LY294002, two specific inhibitors of PI-3K, suggesting a role for PtdIns phosphorylated at the 3-position. PtdIns-specific phospholipase C mimicked GTP hydrolysis as an inducer of NE formation. This induction was dependent on a membrane vesicle subfraction (MV1) that was highly enriched in PtdIns, as determined by heteronuclear two-dimensional NMR spectroscopy. On the basis of these results, we suggest that the MV1 population serves as a source of membranes rich in PtdIns that might facilitate fusion, possibly through the production of the membrane-destabilizing lipid diacylglycerol.