Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan.
The peptidoglycan recognition protein PGRP-LC is a major activator of the imd/Relish pathway in the Drosophila immune response. Three transcripts are generated by alternative splicing of the complex PGRP-LC gene. The encoded transmembrane proteins share an identical intracellular part, but each has a separate extracellular PGRP-domain: x, y, or a. Here we show that two of these isoforms play unique roles in the response to different microorganisms. Using RNA interference in Drosophila mbn-2 cells, we found that PGRP-LCx is the only isoform required to mediate signals from Gram-positive bacteria and purified bacterial peptidoglycan. By contrast, the recognition of Gram-negative bacteria and bacterial lipopolysaccharide requires both PGRP-LCa and LCx. The third isoform, LCy, is expressed at lower levels and may be partially redundant. Two additional PGRP domains in the gene cluster, z and w, are both included in a single transcript of a separate gene, PGRP-LF. Suppression of this transcript does not block the response to any of the microorganisms tested.
Werner
Thomas
T
Umeå Centre for Molecular Pathogenesis, Umeå University, S-901 87 Umeå, Sweden.
Borge-Renberg
Karin
K
Mellroth
Peter
P
Steiner
Hakan
H
Hultmark
Dan
D
D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D004330:Drosophila / Q000187:drug effects / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D029721:Drosophila Proteins / Q000235:genetics*; D017344:Genes, Insect / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000472:pathogenicity; D006094:Gram-Positive Bacteria / Q000472:pathogenicity; D008070:Lipopolysaccharides / Q000494:pharmacology; D005810:Multigene Family / Q000187:drug effects; D010457:Peptidoglycan / Q000494:pharmacology; D034622:RNA Interference
D002352:Carrier Proteins; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein