Elimination of host cell PtdIns(4,5)P2 by bacterial SigD promotes membrane fission during invasion by Salmonella
Elimination of host cell PtdIns(4,5)P2 by bacterial SigD promotes membrane fission during invasion by Salmonella
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DOI：
10.1038/ncb854
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发表时间：
2002-10-01
影响因子：
21.3
通讯作者：
Grinstein, S
中科院分区：
文献类型：
--
作者：
Terebiznik, MR;Vieira, OV;Grinstein, S
沙门氏菌通过肌动蛋白重塑诱导膜皱缩和巨噬细胞吞噬，从而入侵哺乳动物细胞。由于肌醇磷脂是肌动蛋白组装的中心，我们研究了鼠伤寒沙门氏菌入侵HeLa细胞过程中磷脂酰肌醇-4，5-二磷酸(PtdIns(4，5)P-2)的动态变化。在这里，我们发现入侵引起的褶皱的最外面部分在PtdIns(4，5)P-2中有适度的浓缩，但在内陷区域几乎没有PtdIns(4，5)P-2。PtdIns(4，5)P-2的快速消失需要沙门氏菌磷酸酶SigD(也称为SopB)的表达。SigD的缺失显著延迟了内陷膜的分裂，这表明PtdIns(4，5)P-2的消除可能是快速形成含有沙门氏菌的空泡所必需的。SigD的异源表达足以促进PtdIns(4，5)P-2的消失，降低膜骨架的刚性，并诱导质膜内陷和分裂。PtdIns(4，5)P-2的水解可能是膜分裂的共同和基本特征，在几个内化过程中，包括入侵、吞噬和可能的内吞作用。
Salmonella invades mammalian cells by inducing membrane ruffling and macropinocytosis through actin remodelling. Because phosphoinositides are central to actin assembly, we have studied the dynamics of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2) in HeLa cells during invasion by Salmonella typhimurium. Here we show that the outermost parts of the ruffles induced by invasion show a modest enrichment in PtdIns(4,5)P-2, but that PtdIns(4,5)P-2 is virtually absent from the invaginating regions. Rapid disappearance of PtdIns(4,5)P-2 requires the expression of the Salmonella phosphatase SigD (also known as SopB). Deletion of SigD markedly delays fission of the invaginating membranes, indicating that elimination of PtdIns(4,5)P-2 may be required for rapid formation of Salmonella-containing vacuoles. Heterologous expression of SigD is sufficient to promote the disappearance of PtdIns(4,5)P-2, to reduce the rigidity of the membrane skeleton, and to induce plasmalemmal invagination and fission. Hydrolysis of PtdIns(4,5)P-2 may be a common and essential feature of membrane fission during several internalization processes including invasion, phagocytosis and possibly endocytosis.