Zhou K, Pandol S, Bokoch G, Traynor-Kaplan A E
Department of Medicine, University of California San Diego, The Whittier Institute, La Jolla, CA 92037-0983, USA.
J Cell Sci. 1998 Jan;111 ( Pt 2):283-94. doi: 10.1242/jcs.111.2.283.
To understand how phosphatidylinositol 3-kinase (PI3K) modulates cell structure and function, we examined the molecular and cellular defects of a Dictyostelium mutant strain (pik1(Delta)2(Delta)) missing two (DdPIK1 and 2) of three PI3K genes, which are homologues of the mammalian p110 subunit. Levels of [32P]phosphatidylinositol 3, 4 bisphosphate (PI(3,4)P2) and [32P]phosphatidylinositol trisphosphate (PIP3) were reduced in pik1(Delta)2(Delta), which had major defects in morphological and functional correlates of macropinocytosis. This was accompanied by dramatic deficits in a subset of F-actin-enriched structures such as circular ruffles, actin crowns and pseudopodia. Although pik1(Delta)2(Delta) were mobile, they failed to aggregate into streams. Therefore we conclude that PIK1 and 2, possibly through modulation of the levels of PIP3 and PI(3,4)P2, regulate the organization of actin filaments necessary for circular ruffling during macropinocytosis, the extension of pseudopodia and the aggregation of cells into streams, but not the regulation of cell motility.
为了了解磷脂酰肌醇3激酶（PI3K）如何调节细胞结构和功能，我们研究了一种盘基网柄菌突变株（pik1(Delta)2(Delta)）的分子和细胞缺陷，该突变株缺失了三个PI3K基因中的两个（DdPIK1和2），这两个基因是哺乳动物p110亚基的同源物。在pik1(Delta)2(Delta)中，[32P]磷脂酰肌醇3,4-二磷酸（PI(3,4)P2）和[32P]磷脂酰肌醇三磷酸（PIP3）的水平降低，该突变株在巨吞饮作用的形态和功能相关性方面存在主要缺陷。这伴随着富含F-肌动蛋白的结构子集的显著缺陷，如环形皱褶、肌动蛋白冠和伪足。尽管pik1(Delta)2(Delta)能够移动，但它们无法聚集成流。因此，我们得出结论，PIK1和2可能通过调节PIP3和PI(3,4)P2的水平，调节巨吞饮过程中环形皱褶、伪足延伸以及细胞聚集成流所需的肌动蛋白丝的组织，但不调节细胞运动。
