Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, UK.
Dev Comp Immunol. 2012 Sep;38(1):160-8. doi: 10.1016/j.dci.2012.05.004. Epub 2012 May 23.
Zizimin-related (Zir), a Rho guanine nucleotide exchange factor (RhoGEF) homologous to the mammalian Dock-C/Zizimin-related family, was identified in a screen to find new genes involved in the Drosophila melanogaster cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. RhoGEFs activate Rho-family GTPases, which are known to be central regulators of cell migration, spreading and polarity. When a parasitoid wasp is recognized as foreign, multiple layers of circulating immunosurveillance cells (haemocytes) should attach to the egg. In Zir mutants this process is disrupted and lamellocytes, a haemocyte subtype, fail to properly encapsulate the wasp egg. Furthermore, macrophage-like plasmatocytes exhibit a strong reduction in their ability to phagocytise Escherichia coli and Staphylococcus aureus bacteria. During encapsulation and phagocytosis Zir genetically interacts with two Rho-family GTPases, Rac2 and Cdc42. Finally, Zir is dispensable for the humoral immune response against bacteria. We propose that Zir is necessary to activate the Rho-family GTPases Rac2 and Cdc42 during the Drosophila cellular immune response.
Zizimin 相关（Zir）是一种与哺乳动物 Dock-C/Zizimin 家族同源的 Rho 鸟苷三磷酸酶交换因子（RhoGEF），它是在筛选参与 Drosophila melanogaster 细胞免疫反应的新基因时发现的，该免疫反应针对寄生蜂 Leptopilina boulardi 的卵。RhoGEFs 激活 Rho 家族 GTPases，已知这些 GTPases是细胞迁移、扩散和极性的核心调节剂。当寄生蜂被识别为外来时，多层层流免疫监测细胞（血细胞）应该附着在卵上。在 Zir 突变体中，这个过程被打乱，类脂细胞（一种血细胞亚型）不能正确包裹蜂卵。此外，类似于巨噬细胞的浆细胞在吞噬大肠杆菌和金黄色葡萄球菌细菌的能力上表现出强烈的降低。在包裹和吞噬过程中，Zir 在遗传上与两种 Rho 家族 GTPases，Rac2 和 Cdc42 相互作用。最后，Zir 对针对细菌的体液免疫反应是可有可无的。我们提出，Zir 在 Drosophila 细胞免疫反应中激活 Rho 家族 GTPases Rac2 和 Cdc42 是必要的。
