Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide, Sevilla, Spain.
Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
Nat Commun. 2021 Sep 27;12(1):5660. doi: 10.1038/s41467-021-25785-z.
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.
小开放阅读框（smORFs）编码小于 100 个氨基酸的肽是一种神秘且普遍存在的基因类别，在后生动物基因组中发现了数以万计。在这里，我们揭示了一个短的 80 个氨基酸肽（天马座），它增强了 Wingless/Wnt1 蛋白的短程扩散和信号转导。在果蝇翅膀发育过程中，Wingless 具有连续的功能，包括对神经前基因表达和翅膀边缘发育的后期诱导。天马座突变体产生与 Wingless 相似的翅膀边缘缺陷和神经前表达缺失。天马座是分泌的，与 Wingless 共定位和共免疫沉淀，表明它们的物理相互作用。最后，对固定和体内 Wingless 梯度的测量支持 Pegasus 增加 Wingless 扩散以增强其信号转导。我们的结果揭示了 Wingless 信号转导的一个新元素，并阐明了 Wingless 扩散的模式形成作用，同时证实了小开放阅读框肽与具有膜相关功能的已知蛋白的调节之间的联系。
