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PMID: 9716412 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.

Genes & development ·Vol. 12 ·No. 16 ·1998-08-15 ·Pages 2610-22

Axelrod JD, Miller JR, Shulman JM, Moon RT, Perrimon N

Abstract

In Drosophila, planar cell polarity (PCP) signaling is mediated by the receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling also requires Dsh and may utilize DFz2 as a receptor. Using a heterologous system, we show that Dsh is recruited selectively to the membrane by Fz but not DFz2, and this recruitment depends on the DEP domain but not the PDZ domain in Dsh. A mutation in the DEP domain impairs both membrane localization and the function of Dsh in PCP signaling, indicating that translocation is important for function. Further genetic and molecular analyses suggest that conserved domains in Dsh function differently during PCP and Wg signaling, and that divergent intracellular pathways are activated. We propose that Dsh has distinct roles in PCP and Wg signaling. The PCP signal may selectively result in focal Fz activation and asymmetric relocalization of Dsh to the membrane, where Dsh effects cytoskeletal reorganization to orient prehair initiation.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Biological Transport Cell Membrane/metabolism Cell Polarity Cloning, Molecular Cytoplasm/metabolism Dishevelled Proteins Drosophila Drosophila Proteins Frizzled Receptors Membrane Proteins/metabolism Molecular Sequence Data Mutation Phosphoproteins/physiology Proto-Oncogene Proteins/physiology Receptors, G-Protein-Coupled Signal Transduction Wnt1 Protein Xenopus Xenopus Proteins
Chemicals
Adaptor Proteins, Signal Transducing DVL1 protein, Xenopus Dishevelled Proteins Drosophila Proteins Frizzled Receptors Membrane Proteins Phosphoproteins Proto-Oncogene Proteins Receptors, G-Protein-Coupled Wnt1 Protein Xenopus Proteins dsh protein, Drosophila fz protein, Drosophila wg protein, Drosophila
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Axelrod J D
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 USA. [email protected]
Miller J R
Shulman J M
Moon R T
Perrimon N
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.16.2610
Email
[email protected]
Published
1998-08-15
Pages
2610-22
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317102
Subset
IM
Grants
NICHD NIH HHS · HD01036-02 · United States
External Links
PubMed source DOI: 10.1101/gad.12.16.2610 PMC Full Text View journal details
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