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Published 10 April 2006. doi:10.1083/jcb.200510123
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 1, 95-106
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Article

 Internalization is required for proper Wingless signaling in Drosophila melanogaster

Elaine S. Seto3 and Hugo J. Bellen1,2,3

1 Department of Molecular and Human Genetics and 2 Department of Neuroscience, Howard Hughes Medical Institute, and 3 Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030

Correspondence to Hugo J. Bellen: hbellen{at}bcm.tmc.edu

The Wnt–Wingless (Wg) pathway regulates development through precisely controlled signaling. In this study, we show that intracellular trafficking regulates Wg signaling levels. In Drosophila melanogaster cells stimulated with Wg media, dynamin or Rab5 knockdown causes reduced Super8XTOPflash activity, suggesting that internalization and endosomal transport facilitate Wg signaling. In the wing, impaired dynamin function reduces Wg transcription. However, when Wg production is unaffected, extracellular Wg levels are increased. Despite this, target gene expression is reduced, indicating that internalization is also required for efficient Wg signaling in vivo. When endosomal transport is impaired, Wg signaling is similarly reduced. Conversely, the expression of Wg targets is enhanced by increased transport to endosomes or decreased hepatocyte growth factor–regulated tyrosine kinase substrate– mediated transport from endosomes. This increased signaling correlates with greater colocalized Wg, Arrow, and Dishevelled on endosomes. As these data indicate that endosomal transport promotes Wg signaling, our findings suggest that the regulation of endocytosis is a novel mechanism through which Wg signaling levels are determined.

Abbreviations used in this paper: Arm, Armadillo; Arr, Arrow; Ck1a, casein kinase 1a; CMV, cytomegalovirus; Dll, Distal-less; Dsh, Dishevelled; dsRNA, double-stranded RNA; DV, dorsal–ventral; Hrs, hepatocyte growth factor–regulated tyrosine kinase substrate; MVB, multivesicular body; RL, Renilla luciferase; Sens, Senseless; shi, shibire; Wg, Wingless; Wg(ex), extracellular Wg.


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