Document Detail

Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing.
MedLine Citation:
PMID:  16530179     Owner:  NLM     Status:  MEDLINE    
During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.
Anna F Rives; Kate M Rochlin; Marcel Wehrli; Stephanie L Schwartz; Stephen DiNardo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-03-10
Journal Detail:
Title:  Developmental biology     Volume:  293     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-24     Completed Date:  2006-06-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  268-83     Citation Subset:  IM    
University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, Philadelphia, PA 190104-6058, USA.
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MeSH Terms
Drosophila / growth & development*
Drosophila Proteins / metabolism*
Endocytosis / physiology*
Endosomal Sorting Complexes Required for Transport
Frizzled Receptors / metabolism*
Lysosomes / metabolism
Phosphoproteins / physiology
Protein Transport / physiology
Proto-Oncogene Proteins / metabolism*
Receptors, Cell Surface / metabolism*
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction / physiology
Wing / growth & development*
Wnt1 Protein
Grant Support
GM45747/GM/NIGMS NIH HHS; GM67029/GM/NIGMS NIH HHS; R01 GM067029-01/GM/NIGMS NIH HHS; R01 GM067029-02/GM/NIGMS NIH HHS; R01 GM067029-03/GM/NIGMS NIH HHS; R01 GM067029-04/GM/NIGMS NIH HHS; R01 GM067029-05/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Arrow protein, Drosophila; 0/Drosophila Proteins; 0/Endosomal Sorting Complexes Required for Transport; 0/Frizzled Receptors; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Wnt1 Protein; 0/fz2 protein, Drosophila; 0/hepatocyte growth factor-regulated tyrosine kinase substrate; 0/wg protein, Drosophila

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