The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton.
The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton.
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DOI：
10.1091/mbc.e04-03-0272
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发表时间：
2004-12
影响因子：
3.3
通讯作者：
M. Styers;G. Salazar;Rachal Love;A. Peden;A. Kowalczyk;V. Faundez
中科院分区：
文献类型：
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作者：
M. Styers;G. Salazar;Rachal Love;A. Peden;A. Kowalczyk;V. Faundez
细胞骨架网络控制细胞器亚细胞分布和功能。在此，我们描述了中间丝蛋白和接头复合体AP-3之间先前未被怀疑的关联。AP-3和中间丝蛋白作为无微管和肌动蛋白结合蛋白的复合物共同沉积和共免疫沉淀。中间丝细胞骨架的遗传扰动引发了接头AP-3和晚期内吞/溶酶体区室亚细胞分布的变化。伴随着这些结构变化，与AP-3缺失的摩卡细胞相似，缺乏静脉蛋白的成纤维细胞的囊泡锌摄取、细胞器pH、AP-3载物的总量和表面含量都受到损害。然而，转铁蛋白受体（一种独立于AP-3分选的膜蛋白）的总含量和表面水平以及分布在AP-3缺失和vimentin缺失的细胞中保持不变。基于AP-3和波形蛋白缺乏之间的表型趋同，我们预测并记录了摩卡细胞中自噬体含量的降低，这是一种先前在中间丝细胞骨架断裂的细胞中报道的表型。我们的研究结果揭示了中间丝细胞骨架在细胞器/接头定位和接头复合物AP-3调控中的新作用。
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.