PNAS：决定细胞迁移的“美臀”蛋白
圆滚滚的细胞需要分出前后才能开始移动。Johns Hopkins大学的研究人员在模式生物盘基网柄菌(Dictyostelium discoideum)中发现了一种新蛋白，由此阐明了细胞极化的一个重要机制，相关论文发表在六月三十日的美国国家科学院院刊PNAS杂志上。
“Callipygian关闭了那些在细胞前部起作用的蛋白，帮助建立细胞的后部。因此我们根据希腊雕像Venus Callipyge(美臀维纳斯)给它命名，”Johns Hopkins大学的Peter Devreotes教授说。
细胞迁移需要前部和后部协调一致，前部的肌动蛋白纤维形成突起，在前进方向伸出伪足，随后细胞后部被拉向前方。这个过程的不断重复使细胞一步一步接近目的地。不论是前部延伸还是后部缩回都需要通过蛋白表达来实现，细胞必须在正确位置生成特异性的蛋白。
研究人员发现，细胞接到迁移信号之后，许多蛋白会移动到细胞前部与PIP3互作。但Callipygian是向后移动的，而且它也不结合PIP3。“我们对前部蛋白和伪足生成已经比较了解，但细胞后部的形成还是一个谜。因此我们对Callipygian进行了深入研究，”Devreotes说。
细胞要想正确迁移，伪足就只能在前部形成。研究人员发现Callipygian在其中起到了关键性作用，它们在细胞后部聚集可以阻止肌动蛋白纤维生成伪足。“可以说Callipygian关闭了细胞的后部，”文章的第一作者Swaney说。
研究显示，Callipygian通过一个正反馈机制帮助细胞极化。“这种蛋白在细胞极化时移动到细胞后部，在那里建立更大的极性，让更多Callipygian向细胞后部移动，”Devreotes说。
研究人员还分析了这种蛋白的结构，找到了让它向后移动的关键片段。这个片段添加给任何一种蛋白，都能使其向细胞后部移动。研究人员认为，这种操纵蛋白行动方向的能力，将成为研究其他蛋白解析细胞极性的有力武器。
研究人员将继续研究细胞极性蛋白的动态，揭示它们在细胞极化和迁移中起到的作用，帮助人们更好的理解创伤修复和癌转移机制。
推荐原文：Novel protein Callipygian defines the back of migrating Cells.
Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or “clustered,” to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis.
作者：秩名
