Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo.
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.
Chen
Li-Ying
LY
Department of Life Science, Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan 30034, Republic of China.
Wang
Juinn-Chin
JC
Hyvert
Yann
Y
Lin
Hui-Ping
HP
Perrimon
Norbert
N
Imler
Jean-Luc
JL
Hsu
Jui-Chou
JC
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
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