s41467-021-25785-z.pdf (9.59 MB)
Pegasus, a small extracellular peptide enhancing the short-range diffusion of Wingless
Version 2 2023-06-12, 09:57
Version 1 2023-06-10, 00:28
journal contribution
posted on 2023-06-12, 09:57 authored by Emile G Magny, Ana Isabel Platero, Sarah Bishop, Jose Pueyo-Marques, Daniel Aguilar-Hidalgo, Juan Pablo CousoSmall 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.
Funding
Molecular and cellular functions of membrane peptides encoded by small ORFs; G1791; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/N001753/1
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature ResearchExternal DOI
Volume
12Article number
a5660Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-07-27First Open Access (FOA) Date
2021-09-28First Compliant Deposit (FCD) Date
2021-07-26Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC