Rivero F, Köppel B, Peracino B, Bozzaro S, Siegert F, Weijer C J, Schleicher M, Albrecht R, Noegel A A
Max-Planck-Institut für Biochemie, Martinsried, Germany.
J Cell Sci. 1996 Nov;109 ( Pt 11):2679-91. doi: 10.1242/jcs.109.11.2679.
We generated Dictyostelium double mutants lacking the two F-actin crosslinking proteins alpha-actinin and gelation factor by inactivating the corresponding genes via homologous recombination. Here we investigated the consequences of these deficiencies both at the single cell level and at the multicellular stage. We found that loss of both proteins severely affected growth of the mutant cells in shaking suspension, and led to a reduction of cell size from 12 microns in wild-type cells to 9 microns in mutant cells. Moreover the cells did not exhibit the typical polarized morphology of aggregating Dictyostelium cells but had a more rounded cell shape, and also exhibited an increased sensitivity towards osmotic shock and a reduced rate of phagocytosis. Development was heavily impaired and never resulted in the formation of fruiting bodies. Expression of developmentally regulated genes and the final developmental stages that were reached varied, however, with the substrata on which the cells were deposited. On phosphate buffered agar plates the cells were able to form tight aggregates and mounds and to express prespore and prestalk cell specific genes. Under these conditions the cells could perform chemotactic signalling and cell behavior was normal at the onset of multicellular development as revealed by time-lapse video microscopy. Double mutant cells were motile but speed was reduced by approximately 30% as compared to wild type. These changes were reversed by expressing the gelation factor in the mutant cells. We conclude that the actin assemblies that are formed and/or stabilized by both F-actin crosslinking proteins have a protective function during osmotic stress and are essential for proper cell shape and motility.
我们通过同源重组使相应基因失活,构建了缺失两种F-肌动蛋白交联蛋白α-辅肌动蛋白和凝胶化因子的盘基网柄菌双突变体。在此,我们在单细胞水平和多细胞阶段研究了这些缺陷所带来的后果。我们发现,两种蛋白质的缺失严重影响了突变细胞在振荡悬浮液中的生长,并导致细胞大小从野生型细胞的12微米减小到突变细胞的9微米。此外,这些细胞没有呈现出聚集的盘基网柄菌细胞典型的极化形态,而是具有更圆的细胞形状,并且对渗透压休克的敏感性增加,吞噬作用速率降低。发育严重受损,从未形成子实体。然而,发育调控基因的表达以及所达到的最终发育阶段因细胞所接种的底物不同而有所差异。在磷酸盐缓冲琼脂平板上,细胞能够形成紧密的聚集体和丘,并表达前孢子和前柄细胞特异性基因。在这些条件下,细胞能够进行趋化信号传导,延时视频显微镜显示,在多细胞发育开始时细胞行为正常。双突变体细胞具有运动能力,但与野生型相比速度降低了约30%。在突变细胞中表达凝胶化因子可逆转这些变化。我们得出结论,由两种F-肌动蛋白交联蛋白形成和/或稳定的肌动蛋白组装体在渗透压应激期间具有保护作用,并且对于正常的细胞形状和运动能力至关重要。