Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells.
Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells.
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DOI：
10.1083/jcb.201002119
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发表时间：
2010-08-23
期刊：
影响因子：
--
通讯作者：
Parton RG
中科院分区：
文献类型：
--
作者：
Howes MT;Kirkham M;Riches J;Cortese K;Walser PJ;Simpson F;Hill MM;Jones A;Lundmark R;Lindsay MR;Hernandez-Deviez DJ;Hadzic G;McCluskey A;Bashir R;Liu L;Pilch P;McMahon H;Robinson PJ;Hancock JF;Mayor S;Parton RG
定量超微结构分析和蛋白质组学详细CLIC的结构，组成和功能。虽然网格蛋白和小窝蛋白独立的内吞途径的重要性最近出现，这些途径的关键方面仍然未知。使用定量超微结构的方法，我们表明，网格蛋白非依赖性载体（CLIC）占约三倍的体积内化的网格蛋白介导的内吞途径，形成的主要途径参与摄取的流体和散装膜成纤维细胞。对最早的载体的3D形态的电子断层扫描分析表明，它们是多域细胞器，随着它们的成熟形成复杂的分选站。蛋白质组学分析提供了CLIC，细胞粘附周转和迁移之间的直接联系。与此一致，CLIC介导的关键货物蛋白CD 44和Thy-1的内吞作用在迁移的成纤维细胞的前沿被极化，而CLIC的瞬时消融损害了它们的迁移能力。这些研究提供了成纤维细胞中主要内吞途径的第一个定量超微结构分析和分子表征，该途径在迁移细胞的前沿提供快速膜周转。
Quantitative ultrastructural analysis and proteomics detail CLIC structure, composition, and function. Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.
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突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
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作者：
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通讯作者：
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发表时间：
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期刊：
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发表时间：
2008-03-10
期刊：
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