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Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylärbiologi och funktionsgenomik.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylärbiologi och funktionsgenomik.
2007 (engelsk)Inngår i: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 120, nr 7, s. 1209-15Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation.

sted, utgiver, år, opplag, sider
2007. Vol. 120, nr 7, s. 1209-15
Emneord [en]
innate immunity; phenoloxidase; apoptosis; hemocytes; JNK; TNF
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-24444DOI: 10.1242/​jcs.03420ISI: 000245103900010OAI: oai:DiVA.org:su-24444DiVA, id: diva2:197539
Tilgjengelig fra: 2007-09-06 Laget: 2007-08-31 Sist oppdatert: 2017-12-13bibliografisk kontrollert
Inngår i avhandling
1. Genetic and molecular dissection of hemolymph coagulation and melanization in Drosophila melanogaster
Åpne denne publikasjonen i ny fane eller vindu >>Genetic and molecular dissection of hemolymph coagulation and melanization in Drosophila melanogaster
2007 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Injury to epithelial barriers puts metazoans at risk of loss of body fluid and contamination of their body by foreign particles. This risk is even exacerbated in insects, which have an open circulatory system and as a result, quickly need to seal wounds in order to keep a fairly constant internal milieu. Due to paucity of information on biochemical and molecular basis of insects’ clot, we studied how hemolymph of Drosophila melanogaster forms a clot, leading to a better understanding of responses after injury or infection in flies.

By comparing hemolymph of Drosophila after bleeding with that described for an earlier model Galleria mellonella, we showed that a bona fide clot forms in Drosophila. The Drosophila clot is a fibrous network of crosslinked hemolymph proteins, which incorporates blood cells (plasmatocytes) extending shorter cellular processes of filopodia compared to cells outside the clot. Also, some plasmatocytes in the clot show features of apoptotic death while other blood cells (crystal cells) quickly rupture.

The clot sequesters bacteria, as bacteria tethered to clot did not move. Clotting factors isolated include, Hemolectin (Hml) previously implicated in clotting, the immune induced protein Fondue and hemolymph proteins such as apolipophorin 2, fat body protein 1 and larval serum protein 1 γ. Hml mutants were more susceptible to infections when tested in a genetically sensitized background, suggesting that the clot may contribute to innate immunity. Clot also formed in hemolymph without phenoloxidase, an enzyme required for melanization and previously thought to be important for clot formation. However, we found that PO activity strengthens the clot to form a more solid plug.

We found PO activity in clot to be induced in a transcription independent manner by inner membrane phospholipids: phosphatidylserine (PS) and phosphatidylinositol (PI) exposed on dead plasmatocytes and ruptured crystal cells. This is in contrast to induction of the enzyme during infection, which requires microbial components and transcriptional induction. However, both activation of PO in the clot and activation after infection appear to depend on proteases. Surprisingly, neither PS nor PI induced PO activity in the lepidopteran Galleria mellonella, in which the enzyme activity was instead induced by the microbial components peptidoglycan. This result may caution against generalizations of findings from using only one particular insect species. Finally, we found that the rupture of crystal cell during clot formation requires the Drosophila TNF homologue Eiger, JNK homologue Basket and small GTPases. This work therefore adds hemolymph clotting to the responses after injury or infection in flies and largely establishes Drosophila as a model to study coagulation of insect hemolymph. This will lead to a more comprehensive picture of Drosophila immunity with implications for other innate immune systems including our own.

sted, utgiver, år, opplag, sider
Stockholm: Institutionen för molekylärbiologi och funktionsgenomik, 2007. s. 1-30, 36-49
HSV kategori
Forskningsprogram
molekylärbiologi
Identifikatorer
urn:nbn:se:su:diva-7046 (URN)978-91-7155-497-0 (ISBN)
Disputas
2007-09-28, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad
At the time of doctoral defence the following paper was unpublished and had a status as follows: Paper 5: ManuscriptTilgjengelig fra: 2007-09-06 Laget: 2007-08-31 Sist oppdatert: 2012-02-15bibliografisk kontrollert

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