Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide.
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 beta- and gamma-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.
Lázaro-Diéguez
Francisco
F
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Aguado
Carmen
C
Mato
Eugenia
E
Sánchez-Ruíz
Yován
Y
Esteban
Inmaculada
I
Alberch
Jordi
J
Knecht
Erwin
E
Egea
Gustavo
G
D000199:Actins / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000187:drug effects / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020836:Protein Structure, Quaternary; D051381:Rats
D000199:Actins; D047630:Depsipeptides; C057531:jasplakinolide; D046988:Proteasome Endopeptidase Complex