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 activity 1 – 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 problem 4 – 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. Genetic studies in Drosophila combined with structural analyses show that glypicans bind palmitoylate moieties in Wnt ligands, and thus shield Wnt ligands from their aqueous environments to enable them to signal to their distant receptors.

中文翻译：

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磷脂酰肌醇蛋白聚糖屏蔽 Wnt 脂质部分以实现远距离信号传导


相对少量的蛋白质被认为充当形态发生素——在组织内传播的信号分子，以组织组织修复和发育过程中细胞命运的规范。其中包括 Wnt 蛋白，其携带对于信号活动至关重要的棕榈油酸酯部分 1 – 3 。疏水性脂蛋白如何在水性细胞外空间中扩散尚不清楚。已经提出了几种机制，例如涉及脂蛋白颗粒、外泌体或特定分子伴侣的机制来克服这种所谓的 Wnt 溶解度问题 4 – 6 。在这里，我们提供了反对这些模型的证据，并表明 Wnt 脂质受到 Dally 样蛋白 (Dlp) 定义的磷脂酰肌醇蛋白聚糖亚类的核心结构域的屏蔽。结构分析表明，在存在棕榈油酰化肽的情况下，这些磷脂酰肌醇蛋白聚糖会改变构象以形成疏水空间。因此，Dlp家族的磷脂酰肌醇蛋白聚糖保护Wnt蛋白的脂质免受水性环境的影响，并充当Wnt蛋白可被移交给信号受体的储存库。果蝇的遗传研究与结构分析相结合表明，磷脂酰肌醇蛋白聚糖与 Wnt 配体中的棕榈酰酸酯部分结合，从而保护 Wnt 配体免受水环境的影响，使它们能够向远处的受体发出信号。