Cited by 836NF-κB Signaling PathwaysInvertebrate Immune Response MechanismsImmune Response and Inflammation

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A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway

Belvin, Marcia P., Anderson, Kathryn V.·1996·Annual Review of Cell and Developmental Biology

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Abstract

▪ Abstract The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-κB pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-κB pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.

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“Degradation of Cactus and release of Dorsal is controlled by the products of the other ten genes identified at the time, seven acting outside of the embryo (windbeutel, pipe, nudel, gastrulation defective, snake, easter, spaetzle) and three encoding proteins from the syncytial embryo (the transmembrane receptor Toll a…”
Background
The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation
Jordan, K. C., Clegg, N., Blasi, J. A., Morimoto, A. M., Sen, J., Stein, D. S., McNeill, H., Deng, W.-M., Tworoger, M., & Ruohola-Baker, H. (2000) · Nature Genetics · doi:10.1038/74294 · Cited by 98
“Loss of mirr function results in expansion of the ventral expression of pip (ref”
Background
The cAMP-dependent Protein Kinase Site (Ser312) Enhances Dorsal Nuclear Import through Facilitating Nuclear Localization Sequence/Importin Interaction*
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Role of TRAF3 and -6 in the Activation of the NF-κB and JNK Pathways by X-linked Ectodermal Dysplasia Receptor*
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Interaction and Specificity of Rel-related Proteins in Regulating Drosophila Immunity Gene Expression
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Differential Expression and Function of Toll-like Receptors in Langerhans Cells: Comparison with Splenic Dendritic Cells
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“dtd" [ ]> Toll-like receptors (TLR) represent a family of type I transmembrane proteins that are characterized by an extracellular leucine-rich repeat domain and a cytoplasmic domain similar to interleukin (IL)-1 receptor”
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The NF-κB family: Key players during embryonic development and HSC emergence
Espín-Palazón, R., & Traver, D. J. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.03.010 · Cited by 96
Molecular Mechanism That Induces Activation of Spätzle, the Ligand for the Drosophila Toll Receptor
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“…Dorsal in the Drosophila embryo and the activation of NF-κB in cytokine-induced inflammation in mammals led investigators to envision a role for the dorsoventral regulatory cascade in immune defense (St. Johnston and Nusslein-Volhard, 1992; Morisato and Anderson, 1995; Belvin and Anderson, 1996).”
Background
Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo.Preprint
Zhang, H., Levine, M. S., & Ashe, H. L. (2001) · Genes & Development · doi:10.1101/gad.861201 · Cited by 96
“High levels of the Spaetzle ligand lead to optimal activation of the Toll–Dorsal signaling pathway and the induction of the Snail repressor in the presumptive mesoderm of early embryos (for reviews, see Belvin and Anderson 1996; Rusch and Levine 1996).”
Background
Both TLR2 and TLR4 are required for the effective immune response in Staphylococcus aureus-induced experimental murine brain abscess.
Stenzel, W., Soltek, S., Sánchez-Ruiz, M., Akira, S., Miletic, H., Schlüter, D., & Deckert, M. (2008) · American Journal of Pathology · doi:10.2353/ajpath.2008.070567 · Cited by 96
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“In addition, this pathway controls dorsal-ventral polarization during early embryonic development (Belvin and Anderson, 1996; Norris and Manley, 1996; Wasserman, 1993).”
Background
Hypoxia Diminishes Toll-Like Receptor 4 Expression Through Reactive Oxygen Species Generated by Mitochondria in Endothelial Cells
Ishida, I., Kubo, H., Suzuki, S., Suzuki, T., Akashi, S., Inoue, K., Maeda, S., Kikuchi, H., Sasaki, H., & Kondo, T. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.4.2069 · Cited by 85
“Toll is a type I transmembrane receptor, first described in Drosophila, that shares homology to cytoplasmic components of the IL-1 signaling pathway (5).”
Background
Activation of Toll Pathway Is Different between Kuruma Shrimp and Drosophila
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Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3.
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“The intimate relationship between this transcription factor and immune responses is quite ancient in evolutionary terms, since the Drosophila host defense responses to pathogens have been shown to depend on NFkB protein homologues (13).”
Background
Ligand-Receptor and Receptor-Receptor Interactions Act in Concert to Activate Signaling in the Drosophila Toll Pathway*♦
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The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila
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“It is thus reasonable to assume that parasite lineages could adapt to these distinct environments either when transmission is sex biased, either due to unequal host sex-ratio, sex-based social structure, or endogenous susceptibility of one host sex relative to the other [70].”
Background
Mycotoxins reveal connections between plants and animals in apoptosis and ceramide signaling
Gilchrist, D. (1997) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400312 · Cited by 87
“interleukin-1 receptor in mammals (Belvin and Anderson, 1996).”
BackgroundInfluential
Activation of Dendritic Cells by Toll-Like Receptors and C-Type Lectins
Diebold, S. S. (2008) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-71029-5_1 · Cited by 84
“for mediating immune activation upon ligand binding (Belvin and Anderson 1996).”
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The antimicrobial host defense of Drosophila.
Meister, M., Hétru, C., & Hoffmann, J. A. (2000) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-642-59674-2_2 · Cited by 86
Intracellular Proteinases of Invertebrates: Calcium-Dependent and Proteasome/Ubiquitin-Dependent Systems
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Immunity-related genes in Ixodes scapularis—perspectives from genome information
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“…and activator of transcription (STAT) pathways, contribute to the activation of the immune response within arthropods, as previously detailed (Belvin and Anderson, 1996; De Gregorio et al., 2002; Hoffmann and Reichhart, 2002; Govind and Nehm, 2004; Lemaitre, 2004; Rawlings et al., 2004;…”
Background
Monocyte CD14: a multifunctional receptor engaged in apoptosis from both sides
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“Toll is a transmembrane protein that was initially described in Drosophila [48, 49].”
Background
A Dorsal homolog (FcDorsal) in the Chinese shrimp Fenneropenaeus chinensis is responsive to both bacteria and WSSV challenge.
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Identification of a novel relish homolog in Chinese shrimp Fenneropenaeus chinensis and its function in regulating the transcription of antimicrobial peptides.
Li, F.-H., Yan, H., Wang, D.-D., Josepriya, T. J., Li, S.-H., Wang, B., Zhang, J.-Q., & Xiang, J. (2009) · Developmental and Comparative Immunology · doi:10.1016/j.dci.2009.06.001 · Cited by 83
Myeloid Differentiation (MyD)/Growth Arrest DNA Damage (GADD) genes in tumor suppression, immunity and inflammation
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Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2
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“In Drosophila, the immune response to fungal infection is dependent on Toll, a type I transmembrane receptor that shares homology to components of the interleukin-1 signaling pathway (3).”
Background
Presence of Tube isoforms in Litopenaeus vannamei suggests various regulatory patterns of signal transduction in invertebrate NF-κB pathway.
Li, C.-Z., Chen, Y.-X., Weng, S., Li, S., Zuo, H.-L., Yu, X.-Q., Li, H.-Y., He, J.-G., & Xu, X.-P. (2014) · Developmental and Comparative Immunology · doi:10.1016/j.dci.2013.08.012 · Cited by 82
Expression of TLR2 and TLR4 Messenger RNA in the Epithelial Cells of the Nasal Airway
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Specificity Determinants of Proteolytic Processing of Aspergillus PacC Transcription Factor Are Remote from the Processing Site, and Processing Occurs in Yeast If pH Signalling Is Bypassed
Mingot, J., Tilburn, J., Díez, E., Bignell, E., Orejas, M., Widdick, D., Sarkar, S., Brown, C. V., Caddick, M., Espeso, E., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1390 · Cited by 82
Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses.
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Expression of glucocorticoid resistance following social stress requires a second signal
Avitsur, R., Padgett, D. A., Dhabhar, F. S., Stark, J. L., Kramer, K. A., Engler, H., & Sheridan, J. F. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0303090 · Cited by 81
“The Toll protein was first described as a mediator in Drosophila innate immunity [14, 17].”
Background
Molecular characterization of a fish‐specific toll‐like receptor 22 (TLR22) gene from common carp (Cyprinus carpio L.): Evolutionary relationship and induced expression upon immune stimulants
Li, H., Yang, G.-W., Ma, F., Li, T., Yang, H.-T., Rombout, J., & An, L. (2017) · Fish and Shellfish Immunology · doi:10.1016/j.fsi.2017.02.009 · Cited by 81
Physical and functional interactions between Drosophila TRAF2 and Pelle kinase contribute to Dorsal activation
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Drosomycin, an essential component of antifungal defence in Drosophila
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“…of the mammalian liver, and secreted into the haemolymph (Fehlbaum et al., 1994), which is controlled by the Toll signal pathway (Lemaitre et al., 1996), a key immune cascade initially recognized in the establishment of the dorsoventral axis during embryo development (Belvin & Anderson, 1996).”
Background
RNA-seq analysis of Macrobrachium rosenbergii hepatopancreas in response to Vibrio parahaemolyticus infection
Rao, R., Zhu, Y. B., Alinejad, T., Tiruvayipati, S., Thong, K. L., Wang, J., & Bhassu, S. (2015) · Gut Pathogens · doi:10.1186/s13099-015-0052-6 · Cited by 87
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Responses of Host Hemocytes During the Initiation of the Squid-Vibrio Symbiosis
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Porcine TLR2 and TLR6: Identification and Their Involvement in Mycoplasma hyopneumoniae Infection
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Independent evolution of Toll and related genes in insects and mammals
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Background
Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell
Ren, T., Wen, Z.-K., Liu, Z.-M., Liang, Y.-J., Guo, Z., & Xu, L. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.11.4826 · Cited by 78
Activation of the lipopolysaccharide signaling pathway in hepatic transplantation preservation injury12
Tsoulfas, G., Takahashi, Y., Ganster, R. W., Yagnik, G. P., Guo, Z., Fung, J. J., Murase, N., & Geller, D. A. (2002) · Transplantation · doi:10.1097/00007890-200207150-00003 · Cited by 71
Toll-like receptors in female reproductive tract and their menstrual cycle dependent expression.
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“TLRs have been shown to have a key role in the induction of immune and inflammatory responses in mammals (Belvin and Anderson, 1996).”
Background
Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies.
Goto, A., Blandin, S., Royet, J., Reichhart, J., & Levashina, E. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg852 · Cited by 76
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Authors: Belvin, M. P., & Anderson, K. V.
Affiliations: University of California, Berkeley (US)
ORCID: Belvin, Marcia P.
Anderson, Kathryn V.
Venue: Annual Review of Cell and Developmental Biology
Publisher: Annual Reviews
Published: 1996-11
Volume: 12
Issue: 1
Pages: 393-416
ISSN: 1081-0706 (ISSN-L)
1530-8995
DOI: 10.1146/annurev.cellbio.12.1.393
OpenAlex: W2098336582
Cited by: 836
References: 0
Citations by year: 2026: 7 · 2025: 14 · 2024: 24 · 2023: 18 · 2022: 23 · 2021: 22 · 2020: 12 · 2019: 21 · 2018: 23 · 2017: 17 · 2016: 17 · 2015: 24 · 2014: 24 · 2013: 25 · 2012: 19
FWCI: 5.77
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Cell and Developmental Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: Drosophila, Toll receptor, tubes, dorsoventral patterning, embryonic patterning, innate immunity, interleukin-1 receptor, NF-κB, evolution of signaling pathways, plant disease resistance, conserved signaling pathways
MeSH terms: Animals, Drosophila, Signal Transduction, Gene Expression Regulation, Developmental

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A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway

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