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Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan.
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2003 (English)In: J Biol Chem, ISSN 0021-9258, Vol. 278, no 29, 26319-22 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 278, no 29, 26319-22 p.
Keyword [en]
Alternative Splicing, Animals, Carrier Proteins/*genetics, Cell Line, Drosophila/drug effects/*genetics/immunology/microbiology, Drosophila Proteins/*genetics, Genes; Insect/drug effects, Gram-Negative Bacteria/pathogenicity, Gram-Positive Bacteria/pathogenicity, Lipopolysaccharides/pharmacology, Multigene Family/drug effects, Peptidoglycan/pharmacology, RNA Interference
URN: urn:nbn:se:su:diva-20030PubMedID: 12777387OAI: diva2:186555
Available from: 2007-11-21 Created: 2007-11-21 Last updated: 2011-01-13Bibliographically approved
In thesis
1. Peptidoglycan recognition proteins in Drosophila melanogaster
Open this publication in new window or tab >>Peptidoglycan recognition proteins in Drosophila melanogaster
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The fruit fly Drosophila melanogaster is an excellent model organism to study the innate immune response, because insects and mammals share conserved features regarding the recognition and destruction of microorganisms and Drosophila is easily accessible to genetic manipulation. In my present study, I identified a new family of pattern recognition molecules for bacterial peptidoglycan in Drosophila, the Peptidoglycan Recognition Proteins (PGRP). This family of proteins is widespread in the animal kingdom, for instance there are 4 PGRP genes in humans with unknown function. So far, all tested PGRPs (from insects and mammals) have been shown to bind peptidoglycan. In Drosophila, we found and characterized 13 PGRP genes, which fall into two classes: Short PGRPs and Long PGRPs. To the short group belong PGRP-SA, SB1, SB2, SC1A, SC1B, SC2, and SD with short transcripts and predicted extracellular proteins. The long members are PGRP-LA, LB, LC, LD, LE, and LF with long transcripts and predicted intracellular and membrane spanning proteins. Transcripts from the 13 different PGRP genes are present in immune competent organs, and the majority are inducible by infection. The transcriptional regulation of the inducible PGRP genes occurs either via the imd/Relish or in some cases Toll/Dif pathway. My RNAi experiments in mbn-2 cells revealed that the peptidoglycan recognition protein PGRP-LC is a major activator of the imd/Relish pathway. In PGRP-LC deficient mbn-2 cells, Relish signalling is almost entirely blocked. However, the complex PGRP-LC gene generates three alternative splice forms, each of them carrying one of three possible PGRP domains, LCx, LCy, and LCa. I found that in the tissue culture system PGRP-LCa plays a specific role in the recognition of Gram-negative bacteria, while PGRP-LCx is crucial for the recognition of Gram-positive and Gram-negative bacteria, and peptidoglycan. Targeted mutagenesis of the PGRP-LCa isoform in vivo shows that the situation is more complicated than in the cell culture experiments. In conclusion, PGRPs constitute a highly diversified family of proteins, including key players of the innate immune response.

Place, publisher, year, edition, pages
Umeå: Umeå centrum för molekylär patogenes (UCMP) (Medicinska fakulteten), 2004. 58 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 0346-6612-922
Molecular biology, Drosophila, PGRP, peptidoglycan, pattern recognition, imd, Relish, isoform, RNAi, mbn-2, Molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
urn:nbn:se:umu:diva-355 (URN)91-7305-741-X (ISBN)
Public defence
2004-11-30, Sal Betula, NUS, 901 87, Umeå, 09:00 (English)
Available from: 2004-11-09 Created: 2004-11-09 Last updated: 2011-04-11Bibliographically approved

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