Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide

Francisco Lázaro-Diéguez, Carmen Aguado, Eugenia Mato, Yován Sánchez-Ruíz, Inmaculada Esteban, Jordi Alberch, Erwin Knecht, Gustavo Egea

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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 languageEnglish (US)
Pages (from-to)1415-1425
Number of pages11
JournalJournal of cell science
Volume121
Issue number9
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Actin
  • Aggresome
  • Autophagy
  • Cytoskeleton
  • Huntingtin
  • Inclusion bodies
  • Jasplakinolide
  • Microtubules
  • Proteasome

ASJC Scopus subject areas

  • Cell Biology

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