Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless.
Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless.
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DOI：
10.1038/s41467-021-25785-z
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发表时间：
2021-09-27
影响因子：
16.6
通讯作者：
Couso JP
中科院分区：
文献类型：
--
作者：
Magny EG;Platero AI;Bishop SA;Pueyo JI;Aguilar-Hidalgo D;Couso JP
编码少于100个氨基酸的肽的小开放阅读框（smorf）是一个神秘而普遍的基因类别，在后生动物基因组中发现了成千上万个。在这里，我们揭示了一个短的80个氨基酸肽（Pegasus），它可以增强无翼/Wnt1蛋白的短程扩散和信号传导。在果蝇的翅膀发育过程中，无翼具有一系列的功能，包括后期诱导前翼基因表达和翼缘发育。飞马突变体产生翼缘缺陷和前翼表达缺失，与无翼突变体相似。Pegasus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，固定和体内无翼梯度的测量支持Pegasus增加无翼扩散以增强其信号。我们的研究结果揭示了无翼信号传导的一个新元素，阐明了无翼扩散的模式作用，同时证实了小的开放阅读框肽与具有膜相关功能的已知蛋白调控之间的联系。在后生动物基因组中，存在着数千个少于100个密码子的短开放阅读框（smorf），其中大多数具有未知的功能。在这里，作者展示了从果蝇到脊椎动物的smORF是如何产生一种分泌肽的，这种肽可以增强细胞信号蛋白无翼蛋白的扩散。
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. Short open reading frames (smORFs) of less than 100 codons exist in the thousands in metazoan genomes, mostly with yet unknown functions. Here the authors show how a smORF conserved from flies to vertebrates produces a secreted peptide that enhances the diffusion of the cell signalling protein Wingless.
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