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Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless
Emile G Magny1, Ana Isabel Platero1, Sarah A Bishop1,2
1Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide, Sevilla, Spain.
Nature Communications
|September 28, 2021
Summary
Researchers discovered Pegasus, a novel peptide that enhances Wingless/Wnt1 signaling by increasing its diffusion. This finding clarifies the role of Wingless diffusion in development and links small open reading frame peptides to protein regulation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Small Open Reading Frames (smORFs) encode peptides under 100 amino acids and are abundant in metazoan genomes.
- Wingless/Wnt1 signaling is crucial for Drosophila wing development, including proneural gene expression and wing margin formation.
Purpose of the Study:
- To investigate the function of a novel 80 amino-acid peptide, Pegasus, in Wingless/Wnt1 signaling.
- To elucidate the mechanism by which Pegasus influences Wingless/Wnt1 protein diffusion and signaling.
Main Methods:
- Genetic analysis of Pegasus mutants in Drosophila.
- Co-immunoprecipitation and co-localization assays to assess Pegasus-Wingless interaction.
- Measurement of Wingless protein gradients in fixed and in-vivo samples.
Main Results:
- Pegasus peptide enhances short-range diffusion and signaling of Wingless/Wnt1.
- Pegasus mutants exhibit wing margin defects and loss of proneural expression, mirroring Wingless loss-of-function phenotypes.
- Pegasus physically interacts with Wingless, as evidenced by co-localization and co-immunoprecipitation.
- Pegasus increases Wingless diffusion, thereby enhancing its signaling capacity.
Conclusions:
- Pegasus is a novel regulator of Wingless/Wnt1 signaling, acting by modulating protein diffusion.
- The study clarifies the role of Wingless diffusion in developmental patterning.
- Small open reading frame peptides are linked to the regulation of proteins involved in membrane-related functions.
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