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J. Biol. Chem., Vol. 277, Issue 44, 41762-41769, November 1, 2002
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From the Howard Hughes Medical Institute, Department of
Developmental Biology, Stanford University Medical School,
Stanford, California 94305-5323
Secreted Wnt proteins have numerous signaling
functions during development, mediated by Frizzled molecules that act
as Wnt receptors on the cell surface. In the genome of
Drosophila, seven Wnt genes (including
wingless; wg), and five frizzled
genes have been identified. Relatively little is known about signaling
and binding specificities of different Wnt and Frizzled proteins. We
have developed an assay to determine the strength of binding between
membrane-tethered Wnts and ligand binding domains of the Frizzled
receptors. We found a wide spectrum of binding affinities, reflecting
known genetic interactions. Most Wnt proteins can bind to multiple
Frizzleds and vice versa, suggesting redundancy in vivo. In
an extension of these experiments, we tested whether two different
subdomains of the Wg protein would by themselves bind to Frizzled and
generate a biological response. Whereas these two separate
domains are secreted from cells, suggesting that they form
independently folded parts of the protein, they were only able to evoke
a response when co-transfected, indicating that both are required for
function. In addition to the Frizzleds, members of the LRP family
(represented by the arrow gene in Drosophila) are also
necessary for Wnt signal transduction and have been postulated to act
as co-receptors. We have therefore examined whether a soluble form of
the Arrow molecule can bind to Wingless and Frizzled, but no
interactions were detected.
Ligand Receptor Interactions in the Wnt Signaling Pathway in
Drosophila*
*
This work was supported by the Howard Hughes Medical
Institute and National Institutes of Health Grant 1R01GM/CA60388-01.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 650-723-7769;
Fax: 650-723-1399; E-mail: rnusse@cmgm.stanford.edu.
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