Genomes and Genes
Gene Symbol: spz
Alias: CG6134, CT19282, Dmel\CG6134, SPZ, Spz, Spz1, mel(3)7, spatzle, CG6134-PA, CG6134-PB, CG6134-PC, CG6134-PD, CG6134-PI, CG6134-PJ, CG6134-PK, CG6134-PL, protein spaetzle precursor, spaetzle, spazle, spaztle, spz-PA, spz-PB, spz-PC, spz-PD, spz-PI, spz-PJ, spz-PK, spz-PL
Species: fruit fly
- Cho Y, Stevens L, Stein D. Pipe-dependent ventral processing of Easter by Snake is the defining step in Drosophila embryo DV axis formation. Curr Biol. 2010;20:1133-7 pubmed publisher..This observation suggests a mechanism in which the sulfated target of Pipe promotes a productive interaction between Snake and Easter, perhaps by facilitating conformational changes in a complex containing the two proteins. ..
- Narbonne Reveau K, Charroux B, Royet J. Lack of an antibacterial response defect in Drosophila Toll-9 mutant. PLoS ONE. 2011;6:e17470 pubmed publisher..Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection. ..
- Buchon N, Poidevin M, Kwon H, Guillou A, Sottas V, Lee B, et al. A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway. Proc Natl Acad Sci U S A. 2009;106:12442-7 pubmed publisher..It also reveals the conserved role of modular serine proteases in the activation of insect immune reactions. ..
- Tanji T, Hu X, Weber A, Ip Y. Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol. 2007;27:4578-88 pubmed..These results illustrate how specific ligand binding by separate upstream pattern recognition receptors can be translated into a broad-spectrum host response, a hallmark of innate immunity. ..
- Stein D, Nusslein Volhard C. Multiple extracellular activities in Drosophila egg perivitelline fluid are required for establishment of embryonic dorsal-ventral polarity. Cell. 1992;68:429-40 pubmed..This process requires serine proteolytic activity; the injection of serine protease inhibitors into the perivitelline space of wild-type embryos results in the formation of dorsalized embryos...
- Zaidman Rémy A, Hervé M, Poidevin M, Pili Floury S, Kim M, Blanot D, et al. The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity. 2006;24:463-73 pubmed..Our work highlights the key role of PGRPs that encode both sensors and scavengers of peptidoglycan, which modulate the level of the host immune response to the presence of infectious microorganisms. ..
- Levashina E, Ohresser S, Lemaitre B, Imler J. Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin. J Mol Biol. 1998;278:515-27 pubmed..5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene. ..
- Foley E, O Farrell P. Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila. Genes Dev. 2003;17:115-25 pubmed..We propose that NO mediates an early step of the signal transduction pathway, inducing the innate immune response upon natural infection with gram-negative bacteria. ..
- Weber A, Moncrieffe M, Gangloff M, Imler J, Gay N. Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway. J Biol Chem. 2005;280:22793-9 pubmed..These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions. ..
- DeLotto Y, DeLotto R. Proteolytic processing of the Drosophila Spätzle protein by easter generates a dimeric NGF-like molecule with ventralising activity. Mech Dev. 1998;72:141-8 pubmed..Thus Spätzle is a member of a new family of neurotrophin-like signalling molecules in invertebrate development. ..
- Tauszig S, Jouanguy E, Hoffmann J, Imler J. Toll-related receptors and the control of antimicrobial peptide expression in Drosophila. Proc Natl Acad Sci U S A. 2000;97:10520-5 pubmed..confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.
- Bidla G, Dushay M, Theopold U. Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. J Cell Sci. 2007;120:1209-15 pubmed..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. ..
- Ryu J, Ha E, Oh C, Seol J, Brey P, Jin I, et al. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J. 2006;25:3693-701 pubmed..This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity. ..
- Halfon M, Keshishian H. The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo. Dev Biol. 1998;199:164-74 pubmed..Our results suggest that signals received by the epidermis early during muscle development are an important part of the muscle patterning process. ..
- Matskevich A, Quintin J, Ferrandon D. The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function. Eur J Immunol. 2010;40:1244-54 pubmed publisher..We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms. ..
- Ahmad S, Sweeney S, Lee J, Sweeney N, Gao F. Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc Natl Acad Sci U S A. 2009;106:12168-73 pubmed publisher..regulator of the Toll pathway and functions extracellularly, likely by blocking the proteolytic activation of Spaetzle, the Toll receptor ligand. Moreover, Spn5 inhibited activation of the Toll pathway by mutant CHMP2B...
- Vidal S, Khush R, Leulier F, Tzou P, Nakamura M, Lemaitre B. Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses. Genes Dev. 2001;15:1900-12 pubmed..Our genetic demonstration of dTAK1's role in the regulation of Drosophila antimicrobial peptide gene expression suggests an evolutionary conserved role for TAK1 in the activation of Rel/NF-kappaB-mediated host defense reactions. ..
- Tang H, Kambris Z, Lemaitre B, Hashimoto C. Two proteases defining a melanization cascade in the immune system of Drosophila. J Biol Chem. 2006;281:28097-104 pubmed..We have also shown that the melanization reaction activated by MP1 and MP2 plays an important role in augmenting the effectiveness of other immune reactions, thereby promoting resistance of Drosophila to microbial infection. ..
- Ferrandon D, Jung A, Criqui M, Lemaitre B, Uttenweiler Joseph S, Michaut L, et al. A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J. 1998;17:1217-27 pubmed..We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway. ..
- Gordon M, Ayres J, Schneider D, Nusse R. Pathogenesis of listeria-infected Drosophila wntD mutants is associated with elevated levels of the novel immunity gene edin. PLoS Pathog. 2008;4:e1000111 pubmed publisher..These results are consistent with a model in which the regulation of host factors, including edin, must be tightly controlled to avoid the detrimental consequences of having too much or too little activity...
- Tzou P, Reichhart J, Lemaitre B. Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proc Natl Acad Sci U S A. 2002;99:2152-7 pubmed
- Lemaitre B, Nicolas E, Michaut L, Reichhart J, Hoffmann J. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86:973-83 pubmed..Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways. ..
- El Chamy L, Leclerc V, Caldelari I, Reichhart J. Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll. Nat Immunol. 2008;9:1165-70 pubmed publisher..Hence, Persephone defines a parallel proteolytic cascade activated by 'danger signals' such as abnormal proteolytic activities. ..
- Dionne M, Ghori N, Schneider D. Drosophila melanogaster is a genetically tractable model host for Mycobacterium marinum. Infect Immun. 2003;71:3540-50 pubmed..We believe that this system should be a useful genetically tractable model for mycobacterial infection...
- Qiu P, Pan P, Govind S. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development. 1998;125:1909-20 pubmed..These findings are discussed in light of similar hematopoietic functions of Rel/I(kappa)B-family proteins in mice. ..
- Castillejo Lopez C, Hacker U. The serine protease Sp7 is expressed in blood cells and regulates the melanization reaction in Drosophila. Biochem Biophys Res Commun. 2005;338:1075-82 pubmed
- Rancès E, Johnson T, Popovici J, Iturbe Ormaetxe I, Zakir T, Warr C, et al. The toll and Imd pathways are not required for wolbachia-mediated dengue virus interference. J Virol. 2013;87:11945-9 pubmed publisher..This provides additional evidence that the mechanistic basis of Wolbachia-mediated dengue virus blocking in insects is more complex than simple priming of the host insect innate immune system. ..
- Hoffmann A, Funkner A, Neumann P, Juhnke S, Walther M, Schierhorn A, et al. Biophysical characterization of refolded Drosophila Spätzle, a cystine knot protein, reveals distinct properties of three isoforms. J Biol Chem. 2008;283:32598-609 pubmed publisher..Our results suggest that the propeptides stabilize the tertiary structure of the "mature" Spätzle cystine knot. ..
- Anderson K, Nusslein Volhard C. Information for the dorsal--ventral pattern of the Drosophila embryo is stored as maternal mRNA. Nature. 1984;311:223-7 pubmed..Injection of RNA isolated from wild-type embryos into mutants at six loci partially restores dorsal-ventral polarity. For the mutant snake, injection of poly(A)+ RNA restores a complete dorsal-ventral pattern. ..
- Hoffmann J, Kafatos F, Janeway C, Ezekowitz R. Phylogenetic perspectives in innate immunity. Science. 1999;284:1313-8 pubmed..In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity. ..
- Leulier F, Rodriguez A, Khush R, Abrams J, Lemaitre B. The Drosophila caspase Dredd is required to resist gram-negative bacterial infection. EMBO Rep. 2000;1:353-8 pubmed
- Ming M, Obata F, Kuranaga E, Miura M. Persephone/Spätzle pathogen sensors mediate the activation of Toll receptor signaling in response to endogenous danger signals in apoptosis-deficient Drosophila. J Biol Chem. 2014;289:7558-68 pubmed publisher..the key initiator caspase required for apoptosis, produced the active form of the endogenous Toll ligand Spätzle (Spz)...
- Tauszig Delamasure S, Bilak H, Capovilla M, Hoffmann J, Imler J. Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat Immunol. 2002;3:91-7 pubmed..Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals. ..
- Hu X, Yagi Y, Tanji T, Zhou S, Ip Y. Multimerization and interaction of Toll and Spätzle in Drosophila. Proc Natl Acad Sci U S A. 2004;101:9369-74 pubmed..Together, our results suggest that multimerization may be a regulated, essential step for Toll-receptor activation. ..
- Peng J, Zipperlen P, Kubli E. Drosophila sex-peptide stimulates female innate immune system after mating via the Toll and Imd pathways. Curr Biol. 2005;15:1690-4 pubmed..Mating may physically damage females and pathogens may be transferred. Thus, endogenous stimulation of AMP transcription by SP at mating might be considered as a preventive step to encounter putative immunogenic attacks. ..
- Jaaro H, Beck G, Conticello S, Fainzilber M. Evolving better brains: a need for neurotrophins?. Trends Neurosci. 2001;24:79-85 pubmed..Expansion of the genome projects to other invertebrates, such as molluscs and coelenterates, should provide new insights on the molecular correlates of building complex brains. ..
- Meister M, Lemaitre B, Hoffmann J. Antimicrobial peptide defense in Drosophila. Bioessays. 1997;19:1019-26 pubmed..Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review. ..
- Stein D. Pattern formation: The link between ovary and embryo. Curr Biol. 1995;5:1360-3 pubmed
- Rutschmann S, Jung A, Hetru C, Reichhart J, Hoffmann J, Ferrandon D. The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity. 2000;12:569-80 pubmed..We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. ..
- Leulier F, Parquet C, Pili Floury S, Ryu J, Caroff M, Lee W, et al. The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat Immunol. 2003;4:478-84 pubmed..Thus, the ability of Drosophila to discriminate between Gram-positive and Gram-negative bacteria relies on the recognition of specific forms of peptidoglycan. ..
- Tang H, Kambris Z, Lemaitre B, Hashimoto C. A serpin that regulates immune melanization in the respiratory system of Drosophila. Dev Cell. 2008;15:617-26 pubmed publisher..Such signaling between local and systemic immune responses could represent an alarm mechanism that prepares the host in case a pathogen breaches epithelial defenses to invade internal tissues. ..
- Ligoxygakis P, Pelte N, Ji C, Leclerc V, Duvic B, Belvin M, et al. A serpin mutant links Toll activation to melanization in the host defence of Drosophila. EMBO J. 2002;21:6330-7 pubmed..Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults. Microbial challenge induces its removal from the hemolymph through Toll-dependent transcription of an acute phase immune reaction component. ..
- Ligoxygakis P, Bulet P, Reichhart J. Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila. EMBO Rep. 2002;3:666-73 pubmed..18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria. ..
- Leclerc V, Pelte N, El Chamy L, Martinelli C, Ligoxygakis P, Hoffmann J, et al. Prophenoloxidase activation is not required for survival to microbial infections in Drosophila. EMBO Rep. 2006;7:231-5 pubmed..This raises the question with regard to the precise function of phenoloxidase activation in defence, if any. ..
- Lemaitre B, Meister M, Govind S, Georgel P, Steward R, Reichhart J, et al. Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. EMBO J. 1995;14:536-45 pubmed..These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription. ..
- Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner A, Carrera P, et al. FOXO-dependent regulation of innate immune homeostasis. Nature. 2010;463:369-73 pubmed publisher..The sparse production of AMPs in epithelial tissues in response to FOXO may help modulating the defence reaction without harming the host tissues, in particular when animals are suffering from energy shortage or stress. ..
- Defaye A, Evans I, Crozatier M, Wood W, Lemaitre B, Leulier F. Genetic ablation of Drosophila phagocytes reveals their contribution to both development and resistance to bacterial infection. J Innate Immun. 2009;1:322-34 pubmed publisher..We now provide a blueprint of phagocyte importance during both development and innate immune responses in Drosophila. ..
- Bischoff V, Vignal C, Boneca I, Michel T, Hoffmann J, Royet J. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol. 2004;5:1175-80 pubmed..These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex. ..
- Schneider D, Jin Y, Morisato D, Anderson K. A processed form of the Spätzle protein defines dorsal-ventral polarity in the Drosophila embryo. Development. 1994;120:1243-50 pubmed..The purified protein is smaller than the primary translation product of spätzle, suggesting that proteolytic processing of Spätzle on the ventral side of the embryo is required to generate the localized, active form of the protein. ..
- Nicolas E, Reichhart J, Hoffmann J, Lemaitre B. In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila. J Biol Chem. 1998;273:10463-9 pubmed..This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response. ..
- Green C, Levashina E, McKimmie C, Dafforn T, Reichhart J, Gubb D. The necrotic gene in Drosophila corresponds to one of a cluster of three serpin transcripts mapping at 43A1.2. Genetics. 2000;156:1117-27 pubmed..Absence of Spn43Ac, however, gives a clear phenotype, which will allow a mutational analysis of critical features of the molecular structure of serpins. ..
- Morisato D. Spätzle regulates the shape of the Dorsal gradient in the Drosophila embryo. Development. 2001;128:2309-19 pubmed..The production of two Dorsal peaks is addressed by a model that invokes action of a diffusible inhibitor, which is proposed to normally regulate the slope of the Dorsal gradient. ..
- Sorrentino R, Melk J, Govind S. Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila. Genetics. 2004;166:1343-56 pubmed
- Manfruelli P, Reichhart J, Steward R, Hoffmann J, Lemaitre B. A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF. EMBO J. 1999;18:3380-91 pubmed..Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--> Toll-->Cactus-->Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.
- Mulinari S, Hacker U, Castillejo Lopez C. Expression and regulation of Spätzle-processing enzyme in Drosophila. FEBS Lett. 2006;580:5406-10 pubmed..In both cases, Toll is activated by the enzymatically cleaved form of its ligand Spätzle (Spz)...
- Rutschmann S, Kilinc A, Ferrandon D. Cutting edge: the toll pathway is required for resistance to gram-positive bacterial infections in Drosophila. J Immunol. 2002;168:1542-6 pubmed..In this study, we report that the Toll pathway, but not that of immune deficiency, is required for resistance to other Gram-positive bacteria and that this response does not involve Defensin...
- Hecht P, Anderson K. Genetic characterization of tube and pelle, genes required for signaling between Toll and dorsal in the specification of the dorsal-ventral pattern of the Drosophila embryo. Genetics. 1993;135:405-17 pubmed..We discuss the phenotypes of tube-pelle double mutants in the context of whether the two proteins interact directly. ..
- Kambris Z, Brun S, Jang I, Nam H, Romeo Y, Takahashi K, et al. Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation. Curr Biol. 2006;16:808-13 pubmed..with microbial determinants but is rather activated upon binding a cleaved form of the cytokine-like molecule Spatzle (Spz)...
- Ligoxygakis P, Pelte N, Hoffmann J, Reichhart J. Activation of Drosophila Toll during fungal infection by a blood serine protease. Science. 2002;297:114-6 pubmedDrosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette...
- Smith C, DeLotto R. Ventralizing signal determined by protease activation in Drosophila embryogenesis. Nature. 1994;368:548-51 pubmed..Our results support a protease cascade model in which localized activation of uniformly distributed protease proenzymes leads to the spatially restricted production of ligand in the perivitelline space on the ventral side of the embryo. ..
- Takehana A, Yano T, Mita S, Kotani A, Oshima Y, Kurata S. Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO J. 2004;23:4690-700 pubmed..A role for PGRP-LE in the epithelial induction of antimicrobial peptides is also suggested. ..
- Sabatier L, Jouanguy E, Dostert C, Zachary D, Dimarcq J, Bulet P, et al. Pherokine-2 and -3. Eur J Biochem. 2003;270:3398-407 pubmed..Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling. ..
- Charroux B, Royet J. Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response. Proc Natl Acad Sci U S A. 2009;106:9797-802 pubmed publisher..Finally, we show that plasmatocytes are involved in immune surveillance during pupal development, because they prevent bacterial infection that causes pupal lethality...
- Zhu B, Pennack J, McQuilton P, Forero M, Mizuguchi K, Sutcliffe B, et al. Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol. 2008;6:e284 pubmed publisher..This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases...
- Sutcliffe B, Forero M, Zhu B, Robinson I, Hidalgo A. Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila neuromuscular junction. PLoS ONE. 2013;8:e75902 pubmed publisher..The NT family of proteins in Drosophila is formed of DNT1, DNT2 and Spätzle (Spz), with sequence, structural and functional conservation relative to mammalian NTs...
- Shia A, Glittenberg M, Thompson G, Weber A, Reichhart J, Ligoxygakis P. Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes. J Cell Sci. 2009;122:4505-15 pubmed publisher..These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.