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科学家揭示Wnt信号远距离传递的机制
2020-07-23 16:07

英国弗朗西斯·克里克研究所Jean-Paul Vincent和牛津大学E. Yvonne Jones团队合作取得一项新突破。他们发现Glypicans屏蔽Wnt脂质部分以实现其远距离信号传递功能。这一研究成果于2020年7月22日在线发表在《自然》上。

研究人员提供了针对疏水蛋白扩散模型的证据,并表明Wnt脂质被Dally样蛋白(Dlp)Glypicans亚家族的核心结构域所屏蔽。结构分析表明,在棕榈酰化肽存在的情况下,这些甘聚糖改变构象以形成疏水性空间。因此,Dlp家族聚糖可以保护Wnt蛋白的脂质不受水性环境的影响,并可以作为Wnt蛋白将信号传递给受体的储存库。

据悉,人们认为相对少量的蛋白质可以作为成形素,即在组织内流动的信号分子,参与组织修复和发育过程中的细胞命运决定。其中Wnt蛋白属于这类成形素,其包涵的棕榈油酸酯部分对于信号传导活性必不可少。尚不清楚疏水性脂蛋白如何在细胞外空间中扩散。已经提出了几种机制来解释这种所谓的Wnt溶解度问题,例如脂蛋白颗粒、外泌体或特定伴侣机制。

附:英文原文

Title: Glypicans shield the Wnt lipid moiety to enable signalling at a distance

Author: Ian J. McGough, Luca Vecchia, Benjamin Bishop, Tomas Malinauskas, Karen Beckett, Dhira Joshi, Nicola OReilly, Christian Siebold, E. Yvonne Jones, Jean-Paul Vincent

Issue&Volume: 2020-07-22

Abstract: A relatively small number of proteins have been suggested to act as morphogens—signalling molecules that spread within tissues to organize tissue repair and the specification of cell fate during development. Among them are Wnt proteins, which carry a palmitoleate moiety that is essential for signalling activity1,2,3. How a hydrophobic lipoprotein can spread in the aqueous extracellular space is unknown. Several mechanisms, such as those involving lipoprotein particles, exosomes or a specific chaperone, have been proposed to overcome this so-called Wnt solubility problem4,5,6. Here we provide evidence against these models and show that the Wnt lipid is shielded by the core domain of a subclass of glypicans defined by the Dally-like protein (Dlp). Structural analysis shows that, in the presence of palmitoleoylated peptides, these glypicans change conformation to create a hydrophobic space. Thus, glypicans of the Dlp family protect the lipid of Wnt proteins from the aqueous environment and serve as a reservoir from which Wnt proteins can be handed over to signalling receptors.

DOI: 10.1038/s41586-020-2498-z

Source: https://www.nature.com/articles/s41586-020-2498-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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