Abstract
In this study, we report the formation of several cytoplasmic inclusion bodies composed of filamentous actin (F-actin) and generated by experimental treatments using depolymerizing or stabilizing actin toxins in neuronal and non-neuronal mammalian cell lines. The actin-stabilizing toxin jasplakinolide (Jpk) induced, in a microtubule-dependent manner, a single, large F-actin aggregate, which contained β- and γ-actin, ADF/cofilin, cortactin, and the actin nucleator Arp2/3. This aggregate was tightly associated with the Golgi complex and mitochondria, and was surrounded by vimentin intermediate filaments, microtubules and MAP4. Therefore, the Jpk-induced single, large F-actin aggregate fits the established criteria for being considered an aggresome. Lysosomes and/or autophagic vacuoles, proteasomes and microtubules were found to directly participate in the dissolution of this F-actin aggresome. Finally, the model reported here is simple, highly reproducible and reversible, and it provides an opportunity to test pharmacological agents that interfere with the formation, maintenance and/or disappearance of F-actin-enriched pathological inclusion bodies.
Original language | English (US) |
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Pages (from-to) | 1415-1425 |
Number of pages | 11 |
Journal | Journal of cell science |
Volume | 121 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2008 |
Externally published | Yes |
Keywords
- Actin
- Aggresome
- Autophagy
- Cytoskeleton
- Huntingtin
- Inclusion bodies
- Jasplakinolide
- Microtubules
- Proteasome
ASJC Scopus subject areas
- Cell Biology