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Functional Diversity of the Drosophila PGRP-LC Gene Cluster in the Response to Lipopolysaccharide and Peptidoglycan
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
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2003 In: J. Biol. Chem., ISSN 0021-9258, Vol. 278, no 29, 26319-26322. p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 278, no 29, 26319-26322. p.
Identifiers
URN: urn:nbn:se:su:diva-24032OAI: oai:DiVA.org:su-24032DiVA: diva2:196514
Note
Part of urn:nbn:se:su:diva-646Available from: 2005-09-06 Created: 2005-09-06Bibliographically approved
In thesis
1. Peptidoglycan Recognition Proteins: Major Regulators of Drosophila Immunity
Open this publication in new window or tab >>Peptidoglycan Recognition Proteins: Major Regulators of Drosophila Immunity
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

All eukaryotic organisms have an innate immune system characterized by germ-line encoded receptors and effector molecules, which mediate detection and clearance of microbes such as bacteria, fungi, and parasites. VertebrateDrosophila as a genetically tractable organism with a

This thesis concerns the peptidoglycan recognition protein (PGRP) gene family in the fruit fly. The family consists of thirteen genes, of which a few have been reported to be part of the signaling pathways that regulates immune

Data presented show that the putative receptors have affinity for peptidoglycan, but not for lipopolysaccharide, or the fungal cell wall polymer beta-glucan. PGRP-SA, receptor of the Toll pathway, has a preference for

In a search for novel PGRP receptors I found two PGRP proteins that instead displayed enzymatic activity towards peptidoglycan. They are of the N-actylmuramoyl L-alanine amidase type, which degrades peptidoglycan by splittingStaphylococcus aureus peptidoglycan looses its immune elicitor capacity. This is in contrast to lysozyme-degraded peptidoglycan, which isDrosophila PGRPs to be potential enzymes. PGRP-SB1 is the other enzymatic PGRP described within this thesis. It has a moreBacillus megaterium.

In conclusion, receptor PGRP proteins binds bacterial peptidoglycan and triggers immune gene pathways and enzymatic PGRPs have the capacity to reduce the elicitor property of peptidoglycan.

Place, publisher, year, edition, pages
Stockholm: Institutionen för genetik, mikrobiologi och toxikologi, 2005. 58 p.
Keyword
Innate immunity, peptidoglycan recognition protein, PGRP, Toll, Imd, Drosophila immunity
National Category
Pathobiology
Identifiers
urn:nbn:se:su:diva-646 (URN)91-7155-105-0 (ISBN)
Public defence
2005-09-28, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 13:00 (English)
Opponent
Supervisors
Available from: 2005-09-06 Created: 2005-09-06 Last updated: 2010-01-11Bibliographically approved
2. Communicate or die: signalling in Drosophila immunity
Open this publication in new window or tab >>Communicate or die: signalling in Drosophila immunity
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In general the work behind this thesis has revolved around the interesting pattern recognition gene family PGRPs (peptidoglycan recognition proteins). In particular the transmembrane PGRP-LC and to investigate its multifaceted role in the immune response of the fruit fly. As a well characterized model organism living on, and surrounded by, a multitude of microorganisms, Drosophila melanogaster serves as a great tool to gain insights about innate immunity. The two pillars of Drosophila innate immunity are the humoral and the cellular defense. Together they are very potent and can vanquish many infections, but if one of these pillars is damaged, chances are that the defense will collapse and the organism will succumb to the infection.

The initial step in any immune response is to become aware of the pathogen. To accomplish this, innate immunity relies on recognizing common molecular building blocks necessary each group of microorganisms. One such building block is the bacterial cell wall component peptidoglycan. PGRPs are a widely spread gene family, and proteins of this family can bind peptidoglycan. We describe that there are 13 PGRP genes in Drosophila, one these codes for PGRP-LC. As it sits in the cell membrane in any of its three different splice forms, PGRP-LC can bind peptidoglycan, dimerize, and subsequently activate the imd/relish signalling pathway, and thereby trigger a vast production of antimicrobial peptides. These short peptides are the firearms of the humoral response. We identified three new inducible antimicrobial peptide genes, Diptericin B, Attacin C and Attacin D. Analyses of their sequences shed light on the evolution and relationship of these antimicrobial peptides

The antimicrobial peptides are potent weapons, but without a functional cellular response the animal is at loss. Animals lacking blood cells are gravely compromised. It is interesting to find that PGRP-LC is involved at this end of the immune response equation as well. We have found that PGRP-LC is able to activate blood cells and increase numbers of circulating cells, in a JNK (Jun N-terminal kinase) dependent manner. Intriguingly this activation is not dependent on Relish, the NF-kB transcription factor of the Imd/Relish pathway.

PGRP-LC activation funnels into both Imd/Relish and the JNK pathways. When PGRP-LC is lost, it appears that some basal, or background, JNK activation is lost. These effects are very mild, however the animal appears to become more sensitive to additional perturbations in this signalling pathway. This was the starting point when we started to re-evaluate Dredd, the caspase responsible for cleaving and activating Relish. Dredd also contributes to the JNK signalling pathway.

Place, publisher, year, edition, pages
Umeå: Umeå centrum för molekylär patogenes (UCMP) (Medicinska fakulteten), 2008. 63 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1187
Keyword
Drosophila, innate immunity, PGRP-LC, pattern recognition, JNK, antimicrobial peptides
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-1817 (URN)978-91-7264-619-3 (ISBN)
Public defence
2008-09-26, KB3A9, KBC, Umeå Universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2008-09-09 Created: 2008-09-09 Last updated: 2018-01-13Bibliographically approved

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