Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada.
Front Cell Dev Biol. 2014 Sep 18;2:53. doi: 10.3389/fcell.2014.00053. eCollection 2014.
Knowledge of phenotypic changes the cellular prion protein (PrP(C)) contributes to may provide novel avenues for understanding its function. Here we consider data from functional knockout/down studies and protein-protein interaction analyses from the perspective of PrP's relationship to its ancestral ZIP metal ion transporting proteins. When approached in this manner, a role of PrP(C) as a modulator of a complex morphogenetic program that underlies epithelial-to-mesenchymal transition (EMT) emerges. To execute EMT, cells have to master the challenge to shift from cell-cell to cell-substrate modes of adherence. During this process, cell-cell junctions stabilized by E-cadherins are replaced by focal adhesions that mediate cell-substrate contacts. A similar reprogramming occurs during distinct organogenesis events that have been shown to rely on ZIP transporters. A model is presented that sees ZIP transporters, and possibly also PrP(C), affect this balance of adherence modes at both the transcriptional and post-translational levels.
对细胞朊蛋白 (PrP(C)) 表型变化的了解可能为其功能的理解提供新的途径。在这里，我们从 PrP 与其祖先 ZIP 金属离子转运蛋白的关系的角度来考虑功能敲除/下调研究和蛋白质-蛋白质相互作用分析的数据。以这种方式处理时，PrP(C) 作为一种调节上皮-间充质转化 (EMT) 所基于的复杂形态发生程序的调节剂的作用就出现了。为了执行 EMT，细胞必须应对从细胞间到细胞-基质附着模式的转变的挑战。在此过程中，由 E-钙粘蛋白稳定的细胞-细胞连接被介导细胞-基质接触的粘着斑所取代。在已经显示依赖于 ZIP 转运蛋白的不同器官发生事件中，也发生了类似的重编程。提出了一个模型，认为 ZIP 转运蛋白，可能还有 PrP(C)，在转录和翻译后水平上影响这种附着模式的平衡。
