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Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs
Eugenia Piddini1, Francis Marshall, Laurence Dubois
1National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA, UK.
Abstract:
Lysosome-mediated ligand degradation is known to shape morphogen gradients and modulate the activity of various signalling pathways. We have investigated the degradation of Wingless, a Drosophila member of the Wnt family of secreted growth factors. We find that one of its signalling receptors, Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells. However, this is not sufficient for degradation. Indeed, as shown previously, overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor involved in signal transduction, abrogates such stabilization. We provide evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally-like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone cannot lead Wingless all the way from the plasma membrane to a degradative compartment. Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting.
Insights
Wingless (Wnt) protein degradation is essential for signaling. Frizzled2 receptor captures Wingless, but Arrow receptor is required for its lysosomal targeting and degradation.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Lysosome-mediated degradation regulates morphogen gradients and signaling pathways.
- Wingless (Wg), a Drosophila Wnt protein, plays crucial roles in development.
- Receptor-mediated endocytosis is a key mechanism for regulating secreted factors.
Purpose of the Study:
- To investigate the role of Frizzled2 and Arrow receptors in Wingless degradation.
- To elucidate the mechanism of Wingless internalization and lysosomal targeting.
- To understand how receptor interactions modulate Wingless protein stability.
Main Methods:
- Analysis of Wingless protein levels in Drosophila wing imaginal discs and cultured cells.
- Overexpression studies of Frizzled2 and Arrow.
- Immunohistochemistry and cell imaging techniques.
Main Results:
- Frizzled2 receptor mediates Wingless internalization into cells.
- Overexpression of Frizzled2 alone leads to Wingless stabilization.
- Arrow receptor abrogates Frizzled2-induced Wingless stabilization.
- Arrow promotes the lysosomal targeting of Frizzled2-Wingless complexes.
Conclusions:
- Frizzled2 is responsible for Wingless capture and internalization.
- Arrow receptor is essential for directing Wingless to degradative lysosomal compartments.
- Coordinated action of Frizzled2 and Arrow regulates Wingless protein homeostasis and signaling.
