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首页> 外文期刊>Molecular biology of the cell >The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton
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The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton

机译：溶酶体分选机制与中间丝细胞骨架相互作用

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摘要

Cytoskeletal networks control organelle subcellular distribution and function. Herein, we describe a previously unsuspected association between intermediate filament proteins and the adaptor complex AP-3. AP-3 and intermediate filament proteins cosedimented and coimmunoprecipitated as a complex free of microtubule and actin binding proteins. Genetic perturbation of the intermediate filament cytoskeleton triggered changes in the subcellular distribution of the adaptor AP-3 and late endocytic/lysosome compartments. Concomitant with these architectural changes, and similarly to AP-3-null mocha cells, fibroblasts lacking vimentin were compromised in their vesicular zinc uptake, their organellar pH, and their total and surface content of AP-3 cargoes. However, the total content and surface levels, as well as the distribution of the transferrin receptor, a membrane protein whose sorting is AP-3 independent, remained unaltered in both AP-3- and vimentin-null cells. Based on the phenotypic convergence between AP-3 and vimentin deficiencies, we predicted and documented a reduced autophagosome content in mocha cells, a phenotype previously reported in cells with disrupted intermediate filament cytoskeletons. Our results reveal a novel role of the intermediate filament cytoskeleton in organelle/adaptor positioning and in regulation of the adaptor complex AP-3.
机译：细胞骨架网络控制细胞器的亚细胞分布和功能。在本文中，我们描述了中间丝蛋白和衔接子复合物AP-3之间以前未曾想到的关联。 AP-3和中间丝蛋白被沉淀和共免疫沉淀为无微管和肌动蛋白结合蛋白的复合物。中间丝细胞骨架的遗传扰动触发了衔接子AP-3和晚期内吞/溶酶体区室的亚细胞分布的变化。与这些结构变化同时发生的是，类似于AP-3无效的摩卡细胞，缺乏波形蛋白的成纤维细胞的囊泡锌吸收，细胞器pH值以及AP-3货物的总和表面含量受到损害。但是，总含量和表面水平以及转铁蛋白受体（一种不依赖于AP-3进行分选的膜蛋白）的分布在AP-3-和波形蛋白缺失的细胞中均未改变。基于AP-3和波形蛋白缺乏症之间的表型趋同，我们预测并记录了摩卡细胞中自噬体含量的降低，这是先前报道的中间丝细胞骨架被破坏的细胞的表型。我们的结果揭示了中间丝细胞骨架在细胞器/衔接子定位和衔接子复合物AP-3调控中的新作用。

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