Chubb J R, Wilkins A, Thomas G M, Insall R H
MRC Laboratory for Molecular Cell Biology, Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
J Cell Sci. 2000 Feb;113 ( Pt 4):709-19. doi: 10.1242/jcs.113.4.709.
Endocytosis and cell migration both require transient localised remodelling of the cell cortex. Several lines of evidence suggest a key regulatory role in these activities for members of the Ras family of small GTPases. We have generated Dictyostelium cells lacking one member of this family, RasS, and the mutant cells are perturbed in endocytosis and cell migration. Mutant amoebae are defective in phagocytosis and fluid-phase endocytosis and are impaired in growth. Conversely, the rasS(-)cells show an enhanced rate of cell migration, moving three times faster than wild-type controls. The mutant cells display an aberrant morphology, are highly polarised, carry many elongated actin protrusions and show a concomitant decrease in formation of pinocytic crowns on the cell surface. These morphological aberrations are paralleled by changes in the actin cytoskeleton, with a significant proportion of the cortical F-actin relocalised to prominent pseudopodia. Rapid migration and endocytosis appear to be mutually incompatible and it is likely that RasS protein is required to maintain the normal balance between these two actin-dependent processes.
内吞作用和细胞迁移都需要细胞皮层进行短暂的局部重塑。几条证据线索表明，小GTP酶Ras家族成员在这些活动中起关键调节作用。我们构建了缺乏该家族一个成员RasS的盘基网柄菌细胞，突变细胞在内吞作用和细胞迁移方面受到干扰。突变变形虫在吞噬作用和液相内吞作用方面存在缺陷，并且生长受损。相反，rasS(-)细胞显示出细胞迁移速率增强，比野生型对照快三倍。突变细胞呈现异常形态，高度极化，带有许多细长的肌动蛋白突起，并且细胞表面的胞饮小冠形成伴随减少。这些形态异常与肌动蛋白细胞骨架的变化平行，相当一部分皮层F-肌动蛋白重新定位于突出的伪足。快速迁移和内吞作用似乎相互不兼容，并且可能需要RasS蛋白来维持这两个肌动蛋白依赖性过程之间的正常平衡。
