AP-1, but not NF-κB, is required for efficient steroid-triggered cell death in Drosophila

Lehmann, Michael; Jiang, Chenfanfu; Ip, Y. Tony; Thummel, Carl S.

doi:10.1038/sj.cdd.4401003

Cited by 24 publications

(16 citation statements)

References 83 publications

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“…Obp-99, elf-5A, cyclophilin-1, CG10992, CG9760; down: comm3). This finding is in-line with earlier observations that NF-kB activation is not necessary for cell death of salivary glands, thus excluding confounding influences from factors related to autophagy in the salivary glands [28]. …”

Section: Resultssupporting

confidence: 91%

Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

Abdelsadik

Roeder

2010

BMC Genomics

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BackgroundEpithelial and especially mucosal immunity represents the first line of defence against the plethora of potential pathogens trying to invade via the gastrointestinal tract. The salivary glands of the fruit fly are an indispensable part of the gastrointestinal tract, but their contribution to the mucosal immunity has almost completely been neglected. Our major goal was to elucidate if the fly's salivary glands are able to mount an immune response and what the major characteristics of this immune response are.ResultsEctopic activation of the IMD-pathway within the salivary gland cells is able to induce an immune response, indicating that the salivary glands are indeed immune competent. This reaction is characterized by the concurrent expression of numerous antimicrobial peptide genes. In addition, ectopic activation of the salivary gland's immune response induces morphological changes such as dwarfism throughout all developmental stages and a significantly decreased length of the salivary glands themselves. DNA-microarray analyses of the reaction revealed a complex pattern of up- and downregulated genes. Gene ontology analyses of regulated genes revealed a significant increase in genes associated with ribosomal and proteasomal function. On the other hand, genes coding for peptide receptors and some potassium channels are downregulated. In addition, the comparison of the transcriptional events induced following IMD-activation in the trachea and the salivary glands shows also only a small overlap, indicating that the general IMD-activated core transcriptome is rather small and that the tissue specific component of this response is dominating. Among the regulated genes, those that code for signaling associated protease activity are significantly modulated.ConclusionsThe salivary glands are immune-competent and they contribute to the overall intestinal immune system. Although they produce antimicrobial peptides, their overall response is highly tissue-specific. Our analysis indicates that chronic activation of the salivary gland's immune system is costly, as it induces severe reduction in growth throughout development. The IMD-regulated increase in expression levels of the fly's presenilin representatives opens the opportunity to use the salivary glands for studying the physiological and pathophysiological role of these genes in a simple but functional environment.

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Section: Resultssupporting

confidence: 91%

Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

Abdelsadik

Roeder

2010

BMC Genomics

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“…According to the results of competitive RT-PCR procedures, Har-Relish mRNA expression level was lowest on day 1, and it gradually increased until the animal reached the new pupa stage (Figure S6B). This expression pattern is similar to the pattern of Relish expression in D. melanogaster [25]. A 58-kDa protein band was found using an antibody that was specific for Har-Relish, and this band was identical to that predicted for Har-Rel-D (Figure S6C).…”

Section: Resultssupporting

confidence: 75%

A Regulatory Pathway, Ecdysone-Transcription Factor Relish-Cathepsin L, Is Involved in Insect Fat Body Dissociation

Zhang

Liu

et al. 2013

PLoS Genet

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Insect fat body is the organ for intermediary metabolism, comparable to vertebrate liver and adipose tissue. Larval fat body is disintegrated to individual fat body cells and then adult fat body is remodeled at the pupal stage. However, little is known about the dissociation mechanism. We find that the moth Helicoverpa armigera cathepsin L (Har-CL) is expressed heavily in the fat body and is released from fat body cells into the extracellular matrix. The inhibitor and RNAi experiments demonstrate that Har-CL functions in the fat body dissociation in H. armigera. Further, a nuclear protein is identified to be transcription factor Har-Relish, which was found in insect immune response and specifically binds to the promoter of Har-CL gene to regulate its activity. Har-Relish also responds to the steroid hormone ecdysone. Thus, the dissociation of the larval fat body is involved in the hormone (ecdysone)-transcription factor (Relish)-target gene (cathepsin L) regulatory pathway.

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“…For Northern blot analysis, total RNA was extracted from staged 12-to 16-h-old prepupae and pupae. RNA was fractionated by gel electrophoresis, transferred to nylon membranes, and hybridized with radioactive DNA probes as described previously (19). The dLipin probe was a ϳ450-bp PCR product derived from dLipin cDNA GH19076 by using primers with the sequences 5Ј-ATCCCACGTCCCTGATATGC-3Ј and 5Ј-GAC GATGACGAAGCCTCTA-3Ј.…”

Section: Methodsmentioning

confidence: 99%

Lipin Is a Central Regulator of Adipose Tissue Development and Function in Drosophila melanogaster

Ugrankar

Liu

Provaznik

et al. 2011

Molecular and Cellular Biology

104

124

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Lipins are evolutionarily conserved proteins found from yeasts to humans. Mammalian and yeast lipin proteins have been shown to control gene expression and to enzymatically convert phosphatidate to diacylglycerol, an essential precursor in triacylglcerol (TAG) and phospholipid synthesis. Loss of lipin 1 in the mouse, but not in humans, leads to lipodystrophy and fatty liver disease. Here we show that the single lipin orthologue of Drosophila melanogaster (dLipin) is essential for normal adipose tissue (fat body) development and TAG storage. dLipin mutants are characterized by reductions in larval fat body mass, whole-animal TAG content, and lipid droplet size. Individual cells of the underdeveloped fat body are characterized by increased size and ultrastructural defects affecting cell nuclei, mitochondria, and autophagosomes. Under starvation conditions, dLipin is transcriptionally upregulated and functions to promote survival. Together, these data show that dLipin is a central player in lipid and energy metabolism, and they establish Drosophila as a genetic model for further studies of conserved functions of the lipin family of metabolic regulators.Neutral lipids, or triacylglycerols (TAG), are principal energy stores of the eukaryotic cell. Metazoans have evolved specialized tissues that store TAG and make free fatty acids or other derivatives of TAG available to other tissues. Besides having storage functions, these specialized adipose tissues participate in the control of energy homeostasis by producing and releasing hormones and other signaling molecules (21, 26).Severe underdevelopment of the adipose tissue is observed in mice carrying the fatty liver dystrophy (fld) mutation. Lack of fat tissue is associated with transient postnatal accumulation of TAG in the liver, defects in the peripheral nervous system, and insulin resistance (15,16,29). Cloning of the fld gene (renamed lipin 1 [22]) revealed that it encodes a member of an evolutionarily old family of proteins found in a wide variety of eukaryotic organisms, including fungi, plants, and protozoans (22). Both yeast and mammalian lipin proteins act as type 1 phosphatidate phosphatases (PAP1), converting phosphatidate to diacylglycerol (DAG), and as transcriptional coregulators (4, 5, 11, 32). The protein domains responsible for these activities are conserved in lipin proteins of other species, indicating that this functional dichotomy is both evolutionarily old and central to lipin function. DAG produced by mammalian lipin 1 serves as a direct biosynthetic precursor of TAG and phospholipids, whereas the transcriptional coregulator function contributes to the control of genes involved in hepatic ␤-oxidation of fatty acids, the tricarboxylic acid (TCA) cycle, and mitochondrial oxidative phosphorylation (5). While these processes appear to be upregulated by lipin 1, enzymes involved in fatty acid and TAG synthesis are downregulated. In yeast, lipin suppresses genes involved in phospholipid synthesis (32). Loss of lipin in yeast leads to the overgrowth of i...

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AP-1, but not NF-κB, is required for efficient steroid-triggered cell death in Drosophila

Cited by 24 publications

References 83 publications

Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

A Regulatory Pathway, Ecdysone-Transcription Factor Relish-Cathepsin L, Is Involved in Insect Fat Body Dissociation

Lipin Is a Central Regulator of Adipose Tissue Development and Function in Drosophila melanogaster

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