科學家揭示Wnt信號遠距離傳遞的機制

科學家揭示Wnt信號遠距離傳遞的機制

作者：

小柯機器人

發布時間：2020/7/23 16:07:09

英國弗朗西斯·克裡克研究所Jean-Paul Vincent和牛津大學E. Yvonne Jones團隊合作取得一項新突破。他們發現Glypicans屏蔽Wnt脂質部分以實現其遠距離信號傳遞功能。這一研究成果於2020年7月22日在線發表在《自然》上。

研究人員提供了針對疏水蛋白擴散模型的證據，並表明Wnt脂質被Dally樣蛋白（Dlp）Glypicans亞家族的核心結構域所屏蔽。結構分析表明，在棕櫚醯化肽存在的情況下，這些甘聚糖改變構象以形成疏水性空間。因此，Dlp家族聚糖可以保護Wnt蛋白的脂質不受水性環境的影響，並可以作為Wnt蛋白將信號傳遞給受體的儲存庫。

據悉，人們認為相對少量的蛋白質可以作為成形素，即在組織內流動的信號分子，參與組織修復和發育過程中的細胞命運決定。其中Wnt蛋白屬於這類成形素，其包涵的棕櫚油酸酯部分對於信號傳導活性必不可少。尚不清楚疏水性脂蛋白如何在細胞外空間中擴散。已經提出了幾種機制來解釋這種所謂的Wnt溶解度問題，例如脂蛋白顆粒、外泌體或特定伴侶機制。

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