The N-terminal half of the Drosophila Rel/NF-kappaB factor Relish, REL-68, constitutively activates transcription of specific Relish target genes.

The Rel/NF-kappaB transcription factor Relish is a major regulator of the antimicrobial response in Drosophila. Upon immune challenge, Relish is cleaved to generate two fragments, the DNA-binding transcription factor REL-68 and the IkappaB-like REL-49. Using transgenic fly strains we show here that overexpression of REL-68 separately from REL-49 is sufficient to activate strong constitutive transcription of the Diptericin gene, but little constitutive or inducible transcription of Attacin and Cecropin, two other Relish target genes. Their transcription may therefore require additional modifications of Relish. However, phosphorylation of the conserved serine residue S431 is not involved in such modifications. This is unlike p65 and Dorsal, which are modulated by phosphorylation at their homologous site. In contrast to other IkappaB proteins, overexpression of REL-49 had no inhibitory effect on Relish-dependent transcription. Instead, we propose that the C-terminal IkappaB-like domain executes a scaffolding and recruiting function for full activation of Relish.

Rac1 signalling in the Drosophila larval cellular immune response.

The Drosophila larval cellular immune response involves cells (hemocytes) that can be recruited from a hematopoietic organ located behind the brain, as well as a sessile population of cells found just underneath the larval cuticle arranged in a segmental pattern. By using two Rac1 GTPase effector-loop mutants together with epistasis studies, we show that Rac1 requires the Drosophila melanogaster Jun N-terminal kinase Basket (Bsk), as well as stable actin formation to recruit the sessile hemocyte population. We show that actin stabilization is necessary for Rac1-induced hemocyte activation by lowering cofilin (encoded by the twinstar gene tsr) expression in blood cells. Removing Bsk by RNAi suppressed Rac1-induced release of sessile hemocytes. RNAi against Bsk also suppressed Rac1 induction of lamellocytes, a specialized population of hemocytes necessary for the encapsulation of invading pathogens. Furthermore, Rac1 and Bsk are involved in regulating the formation of actin- and focal adhesion kinase (FAK)-rich placodes in hemocytes. Lastly, Rac1 and Bsk are both required for the proper encapsulation of eggs from the parasitoid wasp Leptipolina boulardi. From these data we conclude that Rac1 induces Bsk activity and stable actin formation for cellular immune activation, leading to sessile hemocyte release and an increase in the number of circulating hemocytes.