The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton

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...

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Bibliographic Details
Published in:Molecular biology of the cell 2004-12, Vol.15 (12), p.5369-5382
Main Authors: Styers, Melanie L, Salazar, Gloria, Love, Rachal, Peden, Andrew A, Kowalczyk, Andrew P, Faundez, Victor
Format: Article
Language:English
Subjects:
Adaptor Protein Complex 3 - deficiency
Adaptor Protein Complex 3 - genetics
Adaptor Protein Complex 3 - metabolism
Animals
Cell Line
Cytoskeleton - metabolism
Endosomes - metabolism
Humans
Intermediate Filaments - metabolism
Lysosomes - metabolism
Phenotype
Protein Binding
Rats
Vimentin - deficiency
Vimentin - genetics
Vimentin - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E04-03-0272