Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless

Emile G. Magny, Ana Isabel Platero, Sarah A. Bishop, Jose I. Pueyo, Daniel Aguilar-Hidalgo and Juan Pablo Couso ()
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Emile G. Magny: Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide
Ana Isabel Platero: Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide
Sarah A. Bishop: Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide
Jose I. Pueyo: University of Sussex
Daniel Aguilar-Hidalgo: University of British Columbia
Juan Pablo Couso: Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Small Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are an enigmatic and pervasive gene class, found in the tens of thousands in metazoan genomes. Here we reveal a short 80 amino-acid peptide (Pegasus) which enhances Wingless/Wnt1 protein short-range diffusion and signalling. During Drosophila wing development, Wingless has sequential functions, including late induction of proneural gene expression and wing margin development. Pegasus mutants produce wing margin defects and proneural expression loss similar to those of Wingless. Pegasus is secreted, and co-localizes and co-immunoprecipitates with Wingless, suggesting their physical interaction. Finally, measurements of fixed and in-vivo Wingless gradients support that Pegasus increases Wingless diffusion in order to enhance its signalling. Our results unveil a new element in Wingless signalling and clarify the patterning role of Wingless diffusion, while corroborating the link between small open reading frame peptides, and regulation of known proteins with membrane-related functions.

Date: 2021
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DOI: 10.1038/s41467-021-25785-z

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