期刊
JOURNAL OF CELL SCIENCE
卷 119, 期 17, 页码 3643-3654出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.03147
关键词
vimentin; intermediate filament; adaptor; AP-1; AP-3; Brefeldin A; ARF1
类别
资金
- NIAMS NIH HHS [2T32AR007587-11, 5P30AR042687-090044] Funding Source: Medline
- NINDS NIH HHS [R01 NS42599] Funding Source: Medline
Intermediate filaments are required for proper membrane protein trafficking. However, it remains unclear whether perturbations in vesicular membrane transport result in changes in the architecture of the vimentin cytoskeleton. We find that treatment of cells with Brefeldin A, an inhibitor of specific stages of membrane transport, causes changes in the organization of vimentin filaments. These changes arise from movement of pre-existing filaments. Brefeldin A treatment also leads to alterations in the microtubule cytoskeleton. However, this effect is not observed in cells lacking intermediate filaments, indicating that microtubule bundling is downstream of perturbations in the vimentin cytoskeleton. Brefeldin A-induced changes in vimentin architecture are probably mediated through its effects on ADP-ribosylation factor 1 (ARF1). Expression of a dominant-negative mutant of ARF1 induces BFA-like modifications in vimentin morphology. The BFA-dependent changes in vimentin architecture occurred concurrently with the release of the ARF1-regulated adaptor complexes AP-3 and AP-1 from membranes and adaptor redistribution to vimentin networks. These observations indicate that perturbation of the vesicular membrane transport machinery lead to reciprocal changes in the architecture of vimentin networks.
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