title: Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo.
abstract: BACKGROUND
  The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown.
  
  
  RESULTS
  Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi.
  
  
  CONCLUSIONS
  We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.
authors.affiliation: Department of Life Science, Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan 30034, Republic of China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Chen
authors.forename: Juinn-Chin
authors.initials: JC
authors.lastname: Wang
authors.forename: Yann
authors.initials: Y
authors.lastname: Hyvert
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Lin
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
authors.forename: Jui-Chou
authors.initials: JC
authors.lastname: Hsu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004843:Epistasis, Genetic; D007113:Immunity, Innate / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C499312:Myd88 protein, Drosophila; D010750:Phosphoproteins; D011971:Receptors, Immunologic; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C084727:tub protein, Drosophila; C512628:wek protein, Drosophila; C077938:cact protein, Drosophila