Article
- The EMBO Journal (2004) 23, 100 - 110
- doi:10.1038/sj.emboj.7600033
Published online: 18 December 2003
Subject Categories:
Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning
Huaiyu Suna, Par Towb, Daniel N Chiem, Byron A Foster and Steven A Wasserman
- Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California at San Diego, La Jolla, CA, USA
Correspondence to:
Steven A Wasserman, Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, Rm 301, Mail Code 0634, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA. Tel.: +1 858 822 2408; Fax: +1 858 534 7073; E-mail: stevenw@ucsd.edu
aPresent address: Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
Received 23 September 2003; Accepted 13 November 2003
Abstract
In Drosophila, the Toll pathway establishes the embryonic dorsoventral axis and triggers innate immune responses to infection. The transmembrane receptor Toll acts through three death domain-containing proteins, the kinase Pelle and the adapters Tube and MyD88, in signaling to downstream NF-
B-like transcription factors. Here, we delineate the critical events in the earliest stages of Toll signaling. Mutational studies based on structural modeling reveal that the direct interaction of the bivalent Tube death domain with MyD88 is critical for signaling in vivo. The complex of MyD88 and Tube forms prior to signaling and is localized to the embryonic plasma membrane by MyD88. Upon Toll homodimerization, this complex is rapidly recruited to Toll. Binding of Pelle to the MyD88–Tube complex promotes Pelle activation, leading to degradation of the IB-like inhibitor, Cactus. Together, these experiments convert a linear picture of gene function into a dynamic mechanistic and structural understanding of signaling complex assembly and function.
Keywords:
- death domain,
- dorsoventral patterning,
- IRAK,
- MyD88,
- NF-B,
- Toll,
- Pelle,
- Tube
