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

Magny, Emile G, Platero, Ana Isabel, Bishop, Sarah A, Pueyo, Jose I, Aguilar-Hidalgo, Daniel and Couso, Juan Pablo (2021) Pegasus, a small extracellular peptide enhancing the short-range diffusion of Wingless. Nature Communications, 12. a5660 1-11. ISSN 2041-1723

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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.

Item Type: Article
Keywords: smORFs, Wnt signalling, Wing patterning
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 27 Jul 2021 07:06
Last Modified: 01 Mar 2022 10:36
URI: http://sro.sussex.ac.uk/id/eprint/100785

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Project NameSussex Project NumberFunderFunder Ref
Molecular and cellular functions of membrane peptides encoded by small ORFsG1791BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/N001753/1