GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.

GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.
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DOI:
10.1016/j.cell.2009.07.052
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发表时间:
2009-10-16
期刊:
影响因子:
64.5
通讯作者:
Field SJ
Field SJ
中科院分区:
生物学1区
文献类型:
--
作者:
Dippold HC;Ng MM;Farber-Katz SE;Lee SK;Kerr ML;Peterman MC;Sim R;Wiharto PA;Galbraith KA;Madhavarapu S;Fuchs GJ;Meerloo T;Farquhar MG;Zhou H;Field SJ

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从酵母到人类的高尔基体膜都富含磷脂酰肌醇-4-磷酸(PtdIns(4)P),尽管这种脂质的作用仍然知之甚少。使用蛋白质组脂质结合筛选,我们鉴定了高尔基体蛋白GOLPH 3(也称为GPP 34、GMx 33、MIDAS或酵母Vps 74 p)作为PtdIns(4)P结合蛋白,其依赖PtdIns(4)P进行高尔基体定位。我们进一步表明,GOLPH 3结合非常规肌球蛋白MYO 18 A,从而连接高尔基体的F-肌动蛋白。我们证明,这种联系是必要的正常的高尔基体贩运和形态。证据表明GOLPH 3与PtdIns(4)富含P的反式高尔基体膜和MYO 18 A结合,传递有效小管和囊泡形成所需的张力。因此,这种张力将高尔基体拉伸成荧光显微镜观察到的延伸带状物和电子显微镜观察到的熟悉的扁平形式。
Golgi membranes, from yeast to humans, are uniquely enriched in phosphatidylinositol-4-phosphate (PtdIns(4)P), although the role of this lipid remains poorly understood. Using a proteomic lipid binding screen, we identify the Golgi protein GOLPH3 (also called GPP34, GMx33, MIDAS, or yeast Vps74p) as a PtdIns(4)P-binding protein that depends upon PtdIns(4)P for its Golgi localization. We further show that GOLPH3 binds the unconventional myosin MYO18A, thus connecting the Golgi to F-actin. We demonstrate that this linkage is necessary for normal Golgi trafficking and morphology. The evidence suggests that GOLPH3 binds to PtdIns(4)P-rich trans-Golgi membranes and MYO18A conveying a tensile force required for efficient tubule and vesicle formation. Consequently, this tensile force stretches the Golgi into the extended ribbon observed by fluorescence microscopy and the familiar flattened form observed by electron microscopy.
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