Lázaro-Diéguez Francisco, Aguado Carmen, Mato Eugenia, Sánchez-Ruíz Yován, Esteban Inmaculada, Alberch Jordi, Knecht Erwin, Egea Gustavo
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
J Cell Sci. 2008 May 1;121(Pt 9):1415-25. doi: 10.1242/jcs.017665. Epub 2008 Apr 8.
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.
在本研究中，我们报告了在神经元和非神经元哺乳动物细胞系中，通过使用解聚或稳定肌动蛋白毒素的实验处理，形成了几种由丝状肌动蛋白（F-肌动蛋白）组成的细胞质包涵体。肌动蛋白稳定毒素茉莉素（Jpk）以微管依赖性方式诱导形成单个大的F-肌动蛋白聚集体，其包含β-和γ-肌动蛋白、ADF/丝切蛋白、皮层肌动蛋白以及肌动蛋白成核剂Arp2/3。该聚集体与高尔基体复合物和线粒体紧密相关，并被波形蛋白中间丝、微管和MAP4包围。因此，Jpk诱导的单个大的F-肌动蛋白聚集体符合被视为聚集体的既定标准。发现溶酶体和/或自噬泡、蛋白酶体和微管直接参与了这种F-肌动蛋白聚集体的溶解。最后，这里报道的模型简单、高度可重复且可逆，它为测试干扰富含F-肌动蛋白的病理性包涵体形成、维持和/或消失的药物提供了机会。
