Dippold Holly C, Ng Michelle M, Farber-Katz Suzette E, Lee Sun-Kyung, Kerr Monica L, Peterman Marshall C, Sim Ronald, Wiharto Patricia A, Galbraith Kenneth A, Madhavarapu Swetha, Fuchs Greg J, Meerloo Timo, Farquhar Marilyn G, Zhou Huilin, Field Seth J
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
Cell. 2009 Oct 16;139(2):337-51. doi: 10.1016/j.cell.2009.07.052.
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 on 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.
从酵母到人类，高尔基体膜中磷脂酰肌醇-4-磷酸（PtdIns(4)P）的含量特别丰富，尽管这种脂质的作用仍知之甚少。通过蛋白质组学脂质结合筛选，我们确定高尔基体蛋白GOLPH3（也称为GPP34、GMx33、MIDAS或酵母Vps74p）是一种PtdIns(4)P结合蛋白，其高尔基体定位依赖于PtdIns(4)P。我们进一步表明，GOLPH3与非常规肌球蛋白MYO18A结合，从而将高尔基体与F-肌动蛋白连接起来。我们证明这种联系对于正常的高尔基体运输和形态是必要的。证据表明，GOLPH3与富含PtdIns(4)P的反式高尔基体膜和MYO18A结合，传递有效形成小管和囊泡所需的拉力。因此，这种拉力将高尔基体拉伸成荧光显微镜下观察到的延伸带以及电子显微镜下观察到的常见扁平形态。
