Abstract
The Toll receptor families from insects and vertebrates have structural and evolutionary relationships and it was considered likely that they fulfilled similar functions in their respective organisms. Over the last two years, however, it has become clear that the way in which these receptors recognise pathogens in Drosophila and mammals is quite distinct. The completion of the genome sequences of Drosophila, human and mouse has revealed the presence of nine Toll receptors in the insect and probably ten or 11 in mammals. As shown in Fig. 1, with the exception of dToll9, the Drosophila Tolls are more closely related to each other than they are to the human Toll- like receptors (hTlrs). All Tolls are type 1 transmembrane receptors: they have blocks of a widespread structural motif, the leucine rich repeat in their ectodomains3, a single transmembrane spanning region and a cytoplasmic signalling module, the TollALlR identity region (TIR). The leucine rich repeat is found in many intracellular and extracellular proteins and has structural features that have the potential to evolve a wide range of protein binding specificities.s
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
7. References
S. Tauszig, E. Jouanguy, J.A. Hoffmann and J.L. Imler, Toll-related receptors and the control of antimicrobial peptide expression in Drosophila, P Natl Acad Sci USA 97(19), 10520–10525 (2000).
F.L. Rock, G. Hardiman, J.C. Timans, R.A. Kastelein and J.F. Bazan, A family of human receptors structurally related to Drosophila Toll, P Natl Acad Sci USA 95(2), 588–593 (1998).
S.G.S. Buchanan and N.J. Gay, Structural and functional diversity in the leucine rich repeat family of proteins, Prog Biophys Mol Bio 65(1–2), 1–44 (1996).
M.P. Belvin and K.V. Anderson, A conserved signaling pathway: The Drosophila Toll-Dorsal pathway, Annu Rev Cell Dev Biol 12:393–416 (1996).
A. Stathopoulos, M. Van Drenth, A. Erives, M. Markstein and M. Levine, Whole-genome analysis of dorso-ventral patterning in the Drosophila embryo., Cell, 111:687–701 (2002).
J.L. Imler and J.A. Hoffmann, Toll receptors in innate immunity, Trends Cell Biol 11(7), 304–311 (2001).
S. Akira and H. Hemmi, Recognition of pathogen-associated molecular patterns by TLR family, Immunol Lett 85(2), 85–95 (2003).
S.A. Wasserman, A Conserved Signal-Transduction Pathway Regulating the Activity of the Rel-Like Proteins Dorsal and Nf-Kb, Mol Biol Cell 4(8), 767–771 (1993).
J.D. Thompson, D.G. Higgins and T.J. Gibson, Clustal-W: Improving the Sensitivity of Progressive Multiple Sequence Alignment through Sequence Weighting, Position-Specific Gap Penalties and Weight Matrix Choice, Nucleic Acids Res 22(22), 4673–4680 (1994).
D. Morisato and K.V. Anderson, The Spatzle Gene Encodes a Component of the Extracellular Signaling Pathway Establishing the Dorsal-Ventral Pattern of the Drosophila Embryo, Cell 76(4), 677–688 (1994).
B. Lemaitre, E. Nicolas, L. Michaut, J.M. Reichhart and J.A. Hoffmann, The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults, Cell 86(6), 973–983 (1996).
K. Mizuguchi, J.S. Parker, T.L. Blundell and N.J. Gay, Getting knotted: a model for the structure and activation of Spatzle, Trends Biochem Sci 23(7), 239–242 (1998).
Y. DeLotto and R. DeLotto, Proteolytic processing of the Drosophila Spatzle protein by Easter generates a dimeric NGF-like molecule with ventralising activity, Mech Develop 72(1–2), 141–148 (1998).
A. Weber, S. Tauszig-Delamasure, J. Hoffmann, E. Lelièvre, H. Gascan, K. Ray, M. Morse, J. Imler and N. Gay Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling, Nat Immunol 4:794–800 (2003).
D.S. Schneider, K.L. Hudson, T.Y. Lin and K.V. Anderson, Dominant and Recessive Mutations Define Functional Domains of Toll, a Transmembrane Protein Required for Dorsal Ventral Polarity in the Drosophila Embryo, Gene Dev 5(5), 797–807 (1991).
R. Medzhitov, P. PrestonHurlburt and C.A. Janeway, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity, Nature 388(6640), 394–397 (1997).
M. Gangloff, A.N.R. Weber, R.J. Gibbard and N.J. Gay, Evolutionary relationships, but functional differences, between the Drosophila and human Toll-like receptor families, Biochem Soc T 31:659–663 (2003).
J.S. Parker, K. Mizuguchi and N.J. Gay, A family of proteins related to Spatzle, the toll receptor ligand, are encoded in the Drosophila genome, Proteins 45(1), 71–80 (2001).
X.L.L. He, J.F. Bazan, G. McDermott, J.B. Park, K. Wang, M. Tessier-Lavigne, Z.G. He and K.C. Garcia, Structure of the Nogo receptor ectodomain: A recognition module implicated in myelin inhibition, Neuron 38(2), 177–185 (2003).
E.G. Huizinga, S. Tsuji, R.A.P. Romijn, M.E. Schiphorst, P.G. de Groot, J.J. Sixma and P. Gros, Structures of glycoprotein Ib alpha and its complex with von Willebrand factor A1 domain, Science 297(5584), 1176–1179 (2002).
N. Inohara and G. Nunez, ML-a conserved domain involved in innate immunity and lipid metabolism, Trends Biochem Sci 27(5), 219–221 (2002).
S. Ichikawa, H. Hatanaka, T. Yuuki, N. Iwamoto, S. Kojima, C. Nishiyama, K. Ogura, Y. Okumura and F. Inagaki, Solution structure of Der f 2, the major mite allergen for atopic diseases, J Biol Chem 273(1), 356–60 (1998).
U. Derewenda, J. Li, Z. Derewenda, Z. Dauter, G.A. Mueller, G.S. Rule and D.C. Benjamin, The crystal structure of a major dust mite allergen Der p 2, and its biological implications, J Mol Biol 318(1), 189–97 (2002).
G.A. Mueller, D.C. Benjamin and G.S. Rule, Tertiary structure of the major house dust mite allergen Der p 2: sequential and structural homologies, Biochemistry-Us 37(37), 12707–14 (1998).
G.A. Mueller, A.M. Smith, D.C. Williams, Jr., G.A. Hakkaart, R.C. Aalberse, M.D. Chapman, G.S. Rule and D.C. Benjamin, Expression and secondary structure determination by NMR methods of the major house dust mite allergen Der p 2, J Biol Chem 272(43), 26893–8 (1997).
N. Friedland, H.L. Liou, P. Lobel and A.M. Stock, Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease, Proc Natl Acad Sci U S A 100(5), 2512–7 (2003).
C.S. Wright, S.C. Li and F. Rastinejad, Crystal structure of human GM2-activator protein with a novel beta-cup topology, J Mol Biol 304(3), 411–422 (2000).
C.S. Wright, Q. Zhao and F. Rastinejad, Structural analysis of lipid complexes of GM2-activator protein, J Mol Biol 331(4), 951–64 (2003).
J.Y. Shi, T.L. Blundell and K. Mizuguchi, FUGUE: Sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties, J Mol Biol 310(1), 243–257 (2001).
J.E. Sims, IL-1 and IL-18 receptors, and their extended family, Curr Opin Immunol 14(1), 117–22 (2002).
M. Gangloff, P. Ludidi and N. Gay Structures and motifs involved in Toll signalling. in Toll Receptors (ed. Rich, T.) (Kluwer Academic/Plenum Publishers, New York, 2004).
H.S. Goodridge, E.H. Wilson, W. Harnett, C.C. Campbell, M.M. Harnett and F.Y. Liew, Modulation of macrophage cytokine production by ES-62, a secreted product of the filarial nematode Acanthocheilonema viteae, J Immunol 167(2), 940–945 (2001).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Science + Business Media, Inc.
About this paper
Cite this paper
Gay, N.J., Weber, A.N.R., Gangloff, M. (2005). Activation of Insect and Vertebrate Toll Signaling: From Endogenous Cytokine Ligand to Direct Recognition of Pathogen Patterns. In: Gupta, S., Paul, W.E., Steinman, R. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation X. Advances in Experimental Medicine and Biology, vol 560. Springer, Boston, MA. https://doi.org/10.1007/0-387-24180-9_3
Download citation
DOI: https://doi.org/10.1007/0-387-24180-9_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-24188-3
Online ISBN: 978-0-387-24180-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)