2009/06/29

The site of the uptake and degradation of the Necrotic serpin in Drosophila melanogaster identified.

A new study of the uptake and degradation of the Necrotic serpin in Drosophila melanogaster, carried out by the Functional Genomic group led by David Gubb, was published in the June's edition of PLoS Genetics.

The Necrotic serpin controls a proteolytic cascade which activates the innate immune response to fungal and Gram+ bacterial infections. Following immune-challenge, a proteolytic cascade is activated; it signals through the Toll receptor. Toll activation results in a range of antibiotic peptides being synthesised in the fat-body and exported to the haemolymph. The study demonstrates that Necrotic is not endocytosed in the fat-body, but in the garland and pericardial athrocytes. These cells clear serpins from the haemolymph extremely rapidly. The Necrotic-binding receptor for this process is LpR1, a member of the LDLR family and mutations in LpR1 have a profound effect on the immune response. These results indicate that the scavenging of serpin/proteinase complexes might be a critical step in the regulation of proteolytic cascades.