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Published on: October 13, 2014
arrow encodes an LDL-receptor-related protein essential for Wingless signalling
M Wehrli1, S T Dougan, K Caldwell
1University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
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.
Insights
The arrow gene is essential for Wingless/Wnt signal reception in Drosophila, acting as a transmembrane protein. This finding reveals a conserved role for low-density lipoprotein receptor-related proteins (LRPs) in Wnt signaling pathways.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Wnt signaling is crucial for cell-fate determination and morphogenesis in development.
- Components of the Wingless (Drosophila Wnt) signal transduction cascade, including Frizzled receptors, are known.
- The precise mechanism of Wingless signal reception and transduction across the cell membrane remains incompletely understood.
Purpose of the Study:
- To identify and characterize genes essential for Wingless signaling in Drosophila.
- To elucidate the mechanism of Wingless signal reception at the cellular level.
Main Methods:
- Genetic analysis in Drosophila to identify genes required for Wingless signaling.
- Molecular characterization of the identified gene, 'arrow'.
- Biochemical and structural analysis to determine the function and localization of the Arrow protein.
Main Results:
- The 'arrow' gene is essential for all Wingless signaling events in Drosophila.
- Arrow functions in cells that receive Wingless input and acts upstream of Dishevelled.
- Arrow encodes a single-pass transmembrane protein, homologous to the low-density lipoprotein receptor-related protein (LRP) subfamily (LRP5/6).
Conclusions:
- Arrow acts as a key component in the Wingless/Wnt signal reception complex, potentially with Frizzled proteins.
- This study identifies a novel and conserved function for LRPs in Wingless/Wnt signal reception.
- The findings provide new insights into the molecular mechanisms underlying Wnt pathway activation.
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