Degradation of the necrotic serpin in drosophila and a novel function in the innate immune response in the gut

Resumen

Following immune-challenge by fungal and Gram-positive infections, the Toll receptor is activated, which results in synthesis of antibiotic peptides in the fat-body (the functional equivalent to the human liver). The Necrotic serpin is secreted from the fat-body and released into the haemolymph (the functional equivalent to the human blood plasma), where it modulates the Toll pathway. In this study, Drosophila melanogaster is used to analyse the molecular and physiological mechanisms of serpin uptake and degradation. I demonstrate that Necrotic is removed by the receptor LpR1 from the haemolymph into the garland, and pericardial cells. In both cell types, endocytosed Necrotic is degraded in the lysosome. In addition, I discovered a novel function of Necrotic in the anterior midgut and gastric caecae, where Necrotic translocates to the nucleolus after immune challenge with Gram-positive bacteria. This translocation is probably mediated by the serine protease Jon65Aiv, a putative target of Nec. Moreover, in response to microbial challenge the gastric caecae and the anterior midgut synthesize exosomes, which are secreted into the lumen of the anterior midgut and the gastric caecae.