Drosophila Toll Signalling pathway

Taxon: D. melanogaster
Process: Signalling
Submitter: Abibatou MBODJ and Denis THIEFFRY

Supporting paper: Mbodj, Abibatou and Junion, Guillaume and Brun, Christine and Furlong, Eileen E. M. and Thieffry, Denis (2013). Logical modelling of Drosophila signalling pathways. Molecular BioSystems. 10.1039/c3mb70187e

Model file(s) Description(s)
Toll_Pathway_12Jun2013.zginml GINsim file for Drosophila Toll Signalling pathway
Toll__Pathway_Documentation_11May2013.pdf Drosophila Toll Signalling pathway model documentation

Summary:
Toll was initially discovered as an essential component of the pathway that establishes the dorsal, ventral axis of the early Drosophila embryo. If any component in that genetic pathway is missing, no ventral or lateral cell types develop and the resulting embryos lack all mesoderm and the entire nervous system 1. Fungal and Gram-positive bacterial infections in Drosophila also stimulate the Toll pathway. Activation of Toll leads to recruitment of three cytoplasmic proteins, which are MYD88, Tube and Pelle, to form the signalling complex underneath the cell membrane 2. Subsequently, through interactions via death domains, assembly of the signalling complex containing MYD88, Tube and Pelle occurs 2 3. From this complex, signalling proceeds through the phosphorylation and degradation of the Drosophila IkB factor Cactus. In non signaling conditions, Cactus is bound to Dorsal or Dorsal-related immunity factor (DIF), inhibiting their activity and nuclear localization. Pelle is the only kinase reported for Cactus phosphorylation. After phosphorylation, nuclear translocation of Dorsal/DIF leads to activation of transcription of several sets of target genes 3 4. To reproduce pathway signalling dynamics, we define two initial states corresponding to no signalling conditions (no ligand binding) and to signalling conditions (binding of SPZ to the receptor Toll).

  1. Kathryn V Anderson. Toll signaling pathways in the innate immune response. Current Opinion in Immunology, 12(1):13–19, February 2000. doi:10.1016/s0952-7915(99)00045-x. ↩

  2. Huaiyu Sun, Par Towb, Daniel N Chiem, Byron A Foster, and Steven A Wasserman. Regulated assembly of the toll signaling complex drives drosophila dorsoventral patterning. The EMBO Journal, 23(1):100–110, December 2003. doi:10.1038/sj.emboj.7600033. ↩↩

  3. Takahiro Tanji and Y. Tony Ip. Regulators of the toll and imd pathways in the drosophila innate immune response. Trends in Immunology, 26(4):193–198, April 2005. doi:10.1016/j.it.2005.02.006. ↩↩

  4. Susanna Valanne, Jing-Huan Wang, and Mika Rämet. The drosophila toll signaling pathway. The Journal of Immunology, 186(2):649–656, January 2011. doi:10.4049/jimmunol.1002302. ↩