Abstract Drosophila FKBP39 is the first member of the FK506-binding proteins found in this species. FKBP39 shows the highest similarity to a subfamily of these proteins that comprises one yeast and another insect protein. These FKBPs are characterized by a highly charged N-terminal domain followed by a C-terminal domain that binds the immunosuppressive drug FK506. The cDNA isolated from a library of immune-induced adult flies (GenBank accession number Z46894) shows an open reading frame which codes for a protein with a bipartite domain structure (Theopold et al., 1995): the N-terminus contains two stretches of amino acids with acidic residues, separated by highly basic stretches (Fig. 1). Part of the second basic stretch comprises two overlapping, possible nuclear localization signals. The C-terminal domain shows high similarity to proteins that bind the-immunosuppressive drug FK506 (Gething and Sambrook, 1992; Kay, 1996; see overview, p. 359).
Introduction Chitinase-like proteins (CLPs) are associated with tissue-remodeling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, CLP’s role in tumors is far from clear. Methods Here, we utilize Drosophila melanogaster and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in Ras V12 dysplastic salivary glands. Results and discussion We find one of the Idgf’s members, Idgf3 , is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated via the downstream component, aSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.
Gene list of significantly regulated probes and reciprocal comparison. Transcripts that are significantly altered more than two-fold (|log2FC| ≥ 1, q ≤ 0.05) are shown. 3wDvs1wN represent transcripts regulated upon 3 weeks of diapause compared to 1 week control flies, 3wDvs3wN represent genes regulated in diapause samples with comparison to 3 week old sibling controls, 3wNvs1wN represent genes influenced by aging in 3 week old control flies compared to 1 week old control flies. Significantly inhibited transcripts are highlighted in blue, significantly activated in orange. Links to Flybase, Wikigene, Genecard, NCBI, ENSEMBL and ExPASy databases are included. (XLSX 2131 kb)
List of genes shared between diapause and response to restricted diet in D. melanogaster. We compared our study of three weeks diapause (3wD) to that of an analysis of effects of restricted diet (RF) [145]. Significantly inhibited transcripts are highlighted in blue, significantly activated in orange (for the RF study, genes with q ≤ 0.05 were considered significantly regulated, as was used in original study). Links to Flybase and Genecard databases are included. The Venn diagram summarizes the numbers of significantly regulated genes and how they overlap. (XLSX 173 kb)
Entomopathogenic nematodes (EPNs) of the genera Heterorhabditis
are obligate and lethal insect parasites. In recent years they
have been used increasingly as biological control agents. These
EPNs are symbiotically associated with bacteria of the genera
Photorhabdus. The bacterial symbionts are essential to kill the
host (within 24-48 hours) and digest its tissues to provide
nutrients for themselves as well for expanding nematodes.
Drosophila larvae are suitable insect hosts and part of the
tripartite model system we used before to show the importance
of haemolymph clotting and eicosanoids during the infection. We
used the well-established tripartite model (Drosophila,
nematodes, bacteria), DNA chips and bioinformatic tools to
compare gene expression in non-infected and infected fly
larvae. We focused on the early time point of nematode
infection and therefore infected Drosophila larvae using H.
bacteriophora harbouring GFP-labelled P. luminescens bacteria.
Infected (GFP positive) larvae were collected 6 hours after
infection. We detected approximately 650 genes whose expression
was significantly influenced by nematobacterial infection
caused by H. bacteriophora and P. luminescens. Most of them are
upregulated upon infection including mainly the genes involved
in antimicrobial response and development. Based on Gene
Ontology annotation we identified several pathways, which could
be involved in sealing and repairing the wound caused by
invading nematodes. These results we compared with available
data for other types infection caused by bacteria and parasitic
wasps. Small group of genes were common for all three types of
infection and approximately 25 genes were overlapping in each
pairwise comparison. We focused on the genes expressed in the
hemocytes and fat body, respectively and we subjected selected
candidate genes to functional tests. We tested the effect of
mutations or knockdown of selected genes for the susceptibility
of flies to the nematobacterial infection. The overlap between
the protective genes and genes induced by the nematobacterial
infection was not complete. Therefore, we assume that only a
fraction of the genes involved in the protection of infected
larvae from death are induced by the nematobacterial infection.
Our research is supported by research grants from the Swedish
Research Council (VR-NT 2010-5118), the Swedish Foundation for
International Cooperation in Research and Higher Education
(STINT) and by grant from Ministry of Agriculture of Czech
Republic (NAZV-KUS QJ1210047).
Abstract Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via Ras V12 -overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals, induced hypertrophy and stress accumulation. This allowed us to decipher a novel, spatio-temporally regulated interaction between the JNK-stress response and a genuine tissue-autonomous immune response. Central to this interaction is the direct inhibition of JNK-signalling by the antimicrobial peptide Drosomycin, which blocks programmed cell death and prevents recognition of the stressed tissue by the systemic immune response. While this mechanism might allow growing salivary glands to cope with temporary stress, continuous expression of Drosomycin favors survival of unrestricted, hypertrophic Ras V12 -glands. Our findings indicate the necessity for refined therapeutic approaches that fundamentally acknowledge detrimental effects that stimulated immune responses have on tissues coping with damage and stress.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
