Delineating a Pathogen Response Pathway in Drosophila

Science's STKE  01 Feb 2005:
Vol. 2005, Issue 269, pp. tw44
DOI: 10.1126/stke.2692005tw44

Host organisms initiate a defense response to bacterial infection through innate immune receptors that recognize microbial molecules. In Drosophila, a transmembrane protein of the peptidoglycan-recognition protein family called PGRP-LC responds to certain microbial peptides by initiating a signaling cascade that activates genes with antibacterial action. Although genetic analysis suggests that the pathway involves the death-domain protein Imd and Relish, a transcription factor of the NF-κB family, molecular details of the cascade have not been determined. By expressing PGRP-LC in cultured Drosophila cells, Choe et al. found that the receptor requires its membrane-proximal cytoplasmic region either to homodimerize or to form heterodimers with other receptor isoforms. Expression of PGRP-LC and Imd deletion mutants revealed interaction between the receptor cytoplasmic tail and the N terminus of Imd, although the interaction may not be direct. The pathway appears similar to a signaling pathway initiated by mammalian Toll-like receptors that likewise function in pathogen recognition and also form a complex with the death-domain protein MyD88 to activate an IκB kinase complex.

K.-M. Choe, H. Lee, K. V. Anderson, Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Proc. Natl. Acad. Sci. U.S.A. 102, 1122-1126 (2005). [Abstract] [Full Text]