The RhoGEF Zizimin-related acts in the Drosophila cellular immune response via the Rho GTPases Rac2 and Cdc42

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.

► The RhoGEF Zizimin-related (Zir) is necessary for a proper cellular immune response.
► Zir is not necessary for proper regulation of the humoral response.
► Zir signals upstream of both Cdc42 and Rac2 during ecapsulation of parasitoid wasp eggs and phagocytosis of bacteria.
► Zir is necessary for proper lamellocyte spreading during encapsulation.