Abstract
The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.
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Acknowledgements
G. Campbell, G. Struhl, F. Diaz-Benjumea, S. Cohen, R. Goto-Mandeville, E. Bieschke and B. Calvi provided insightful suggestions and help along the way. The free exchange of information with the Skarnes lab is acknowledged. The manuscript was improved by comments from N. Erdeniz, P. Klein, B. Wilder and the DiNardo lab. Material provided by J. Szidonya, the Bloomington Stock Center and Berkeley Drosophila Genome Project was of great importance. Supported by the Swiss National Science Foundation (M.W.), NIH (A.T. and S.D.) and American Cancer Society (S.D.).
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Wehrli, M., Dougan, S., Caldwell, K. et al. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407, 527–530 (2000). https://doi.org/10.1038/35035110
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DOI: https://doi.org/10.1038/35035110
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