Trafficking of prion proteins through a caveolae-mediated endosomal pathway.
Trafficking of prion proteins through a caveolae-mediated endosomal pathway.
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DOI：
10.1083/jcb.200304140
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发表时间：
2003-08-18
影响因子：
7.8
通讯作者：
Prusiner, Stanley B
中科院分区：
文献类型：
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作者：
Peters, Peter J;Mironov, Alexander Jr;Peretz, David;van Donselaar, Elly;Leclerc, Estelle;Erpel, Susanne;DeArmond, Stephen J;Burton, Dennis R;Williamson, R Anthony;Vey, Martin;Prusiner, Stanley B
为了了解细胞朊蛋白（PrPC）的翻译后转换到其病理构象，重要的是要确定胞内运输途径的PrPC内膜系统。我们研究了本地化和内化的PrPC在CHO细胞使用冷冻免疫金电子显微镜。在稳定状态下，PrPC富集在小窝在TGN和质膜和内吞小窝的互连链。蛋白A-金颗粒特异性结合活细胞上的PrPC。这些复合物被交付通过小窝的pericentriolar区域和通过非经典的，小窝包含早期内吞结构的晚期内体/溶酶体，从而绕过由网格蛋白包被的囊泡介导的内化途径。内吞的PrPC含有小窝不针对ER和高尔基复合体。PrPC的吸收和降解是缓慢和敏感的菲律宾。这种小窝依赖的内吞途径没有观察到其他几个糖基磷脂酰肌醇（GPI）锚定蛋白。我们建议，这种非经典的内吞途径是可能的，以确定PrPC转换的亚细胞位置。
To understand the posttranslational conversion of the cellular prion protein (PrPC) to its pathologic conformation, it is important to define the intracellular trafficking pathway of PrPC within the endomembrane system. We studied the localization and internalization of PrPC in CHO cells using cryoimmunogold electron microscopy. At steady state, PrPC was enriched in caveolae both at the TGN and plasma membrane and in interconnecting chains of endocytic caveolae. Protein A–gold particles bound specifically to PrPC on live cells. These complexes were delivered via caveolae to the pericentriolar region and via nonclassical, caveolae-containing early endocytic structures to late endosomes/lysosomes, thereby bypassing the internalization pathway mediated by clathrin-coated vesicles. Endocytosed PrPC-containing caveolae were not directed to the ER and Golgi complex. Uptake of caveolae and degradation of PrPC was slow and sensitive to filipin. This caveolae-dependent endocytic pathway was not observed for several other glycosylphosphatidyl inositol (GPI)-anchored proteins. We propose that this nonclassical endocytic pathway is likely to determine the subcellular location of PrPC conversion.