Clearance of a Hirano body-like F-actin aggresome generated by jasplakinolide.
We have reported in a variety of mammalian cells the reversible formation of a filamentous actin (F-actin)-enriched aggresome generated by the actin toxin jasplakinolide (Lázaro-Diéguez et al., J Cell Sci 2008; 121:1415-25). Notably, this F-actin aggresome (FAG) resembles in many aspects the pathological Hirano body, which frequently appears in some diseases such as Alzheimer's and alcoholism. Using selective inhibitors, we examined the molecular and subcellular mechanisms that participate in the clearance of the FAG. Chaperones, microtubules, proteasomes and autophagosomes all actively participate to eliminate the FAG. Here we compile and compare these results and discuss the involvement of each process. Because of its simplicity and high reproducibility, our cellular model could help to test pharmacological agents designed to interfere with the mechanisms involved in the clearance of intracellular bodies and, in particular, of those enriched in F-actin.
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Francisco
F
Lázaro-Diéguez
Erwin
E
Knecht
Gustavo
G
Egea
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000473:pathology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D047630:Depsipeptides / Q000502:physiology*; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D014709:Vero Cells
D000199:Actins; D047630:Depsipeptides; C057531:jasplakinolide