An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis
An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis
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DOI：
10.1083/jcb.200909025
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发表时间：
2009-11-30
影响因子：
7.8
通讯作者：
Grinstein, Sergio
中科院分区：
文献类型：
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作者：
Fairn, Gregory D.;Ogata, Koji;Grinstein, Sergio
由磷脂酰肌醇（PI）4-磷酸（PI 4P）5-激酶（PI 5 K）合成的质膜磷脂酰肌醇（PI）4，5-二磷酸（PI 4，5 P（2））是驱动趋化性和吞噬作用的肌动蛋白聚合的关键。我们研究了PIP 5 K靶向膜的方法及其在吞噬体形成过程中的命运。同源性建模显示，所有PIP 5 K亚型都具有带正电荷的面。连同基板结合环，这聚阳离子表面提出构成一个符合检测器，目标PIP 5 Ks的质膜。因此，表面电荷的操纵使PIP 5 Ks从质膜移位。在颗粒吞噬，PIP 5 Ks脱离形成吞噬体的表面电荷在这些网站减少。排除表面电荷的变化导致PIP 5 K保持与吞噬体杯相关联。化学诱导的PIP 5 K-γ滞留阻止了PI 4，5 P（2）的消失和吞噬体的形成。我们的结论是，一个静电开关机制调节协会/解离的PIP 5 Ks从膜在吞噬和可能的其他过程。
Plasmalemmal phosphatidylinositol (PI) 4,5-bisphosphate (PI4,5P(2)) synthesized by PI 4-phosphate (PI4P) 5-kinase (PIP5K) is key to the polymerization of actin that drives chemotaxis and phagocytosis. We investigated the means whereby PIP5K is targeted to the membrane and its fate during phagosome formation. Homology modeling revealed that all PIP5K isoforms feature a positively charged face. Together with the substrate-binding loop, this polycationic surface is proposed to constitute a coincidence detector that targets PIP5Ks to the plasmalemma. Accordingly, manipulation of the surface charge displaced PIP5Ks from the plasma membrane. During particle engulfment, PIP5Ks detached from forming phagosomes as the surface charge at these sites decreased. Precluding the change in surface charge caused the PIP5Ks to remain associated with the phagosomal cup. Chemically induced retention of PIP5K-gamma prevented the disappearance of PI4,5P(2) and aborted phagosome formation. We conclude that a bistable electrostatic switch mechanism regulates the association/dissociation of PIP5Ks from the membrane during phagocytosis and likely other processes.