Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK.
J Cell Sci. 2012 May 15;125(Pt 10):2457-65. doi: 10.1242/jcs.100966. Epub 2012 Feb 24.
Dock (dedicator of cytokinesis) proteins represent a family of guanine nucleotide exchange factors (GEFs) that include the well-studied Dock180 family and the poorly characterised zizimin family. Our current understanding of Dock180 function is that it regulates Rho small GTPases and thus has a role in a number of cell processes, including cell migration, development and division. Here, we use a tractable model for cell motility research, Dictyostelium discoideum, to help elucidate the role of the related zizimin proteins. We show that gene ablation of zizA causes no change in development, whereas ablation of zizB gives rise to an aberrant developmental morphology and a reduction in cell directionality and velocity, and altered cell shape. Fluorescently labelled ZizA protein associates with the microtubule-organising centre (MTOC), whereas ZizB is enriched in the cortex. Overexpression of ZizB also causes an increase in the number of filopodia and a partial inhibition of cytokinesis. Analysis of ZizB protein binding partners shows that it interacts with Rac1a and a range of actin-associated proteins. In conclusion, our work provides insight into the molecular and cellular functions of zizimin GEF proteins, which are shown to have a role in cell movement, filopodia formation and cytokinesis.
Dock（胞质分裂的奉献者）蛋白代表了一类鸟嘌呤核苷酸交换因子（GEFs），包括研究充分的 Dock180 家族和研究不足的 zizimin 家族。我们目前对 Dock180 功能的理解是，它调节 Rho 小分子 GTPases，因此在许多细胞过程中发挥作用，包括细胞迁移、发育和分裂。在这里，我们使用一种可用于细胞运动研究的模式生物，Dictyostelium discoideum，来帮助阐明相关 zizimin 蛋白的作用。我们表明，zizA 基因缺失不会改变发育，而 zizB 基因缺失会导致发育形态异常、细胞方向性和速度降低以及细胞形状改变。荧光标记的 ZizA 蛋白与微管组织中心（MTOC）相关联，而 ZizB 则在皮层中富集。ZizB 的过表达也会导致更多的丝状伪足的形成，并部分抑制胞质分裂。对 ZizB 蛋白结合伴侣的分析表明，它与 Rac1a 和一系列与肌动蛋白相关的蛋白相互作用。总之，我们的工作深入了解了 zizimin GEF 蛋白的分子和细胞功能，这些蛋白在细胞运动、丝状伪足形成和胞质分裂中发挥作用。
