Autophagy-mediated clearance of aggresomes is not a universal phenomenon.
Autophagy-mediated clearance of aggresomes is not a universal phenomenon.
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DOI：
10.1093/hmg/ddn157
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发表时间：
2008-08
影响因子：
3.5
通讯作者：
E. Wong;Jeanne M. M. Tan-Jeanne-M.-M.-Tan-2245821;Wen-E Soong;K. Hussein;N. Nukina;V. Dawson;T. Dawson;A. Cuervo;K. Lim
中科院分区：
文献类型：
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作者：
E. Wong;Jeanne M. M. Tan-Jeanne-M.-M.-Tan-2245821;Wen-E Soong;K. Hussein;N. Nukina;V. Dawson;T. Dawson;A. Cuervo;K. Lim
聚集体是近核包涵体，被认为是通过自噬途径处理蛋白质聚集体的集结地。为了研究聚合体的组成是否会影响自噬对其的清除，我们在培养细胞中异位表达了多种易于聚集的蛋白质，以产生蛋白质含量不同的聚合体。我们发现，表达突变的亨廷顿蛋白或突变的tau蛋白或共表达synphilin-1和α -突触核蛋白的细胞产生的聚集体可以被自噬清除，而表达AIMP2 （p38）或突变的desmin的细胞产生的聚集体显然对自噬清除有抗性。值得注意的是，AIMP2 （p38）和desmin阳性包涵体不能招募自噬/溶酶体系统的关键成分。然而，通过改变内含物的组成，“抗自噬”的聚合体可以变成“易自噬”。综上所述，我们的研究结果表明，并非所有的聚合体都能有效地启动自噬清除，并强调了对所谓的非歧视性途径的一定程度的选择性。
Aggresomes are juxtanuclear inclusion bodies that have been proposed to act as staging grounds for the disposal of protein aggregates via the autophagic route. To examine whether the composition of an aggresome influences its clearance by autophagy, we ectopically expressed a variety of aggregation-prone proteins in cultured cells to generate aggresomes that differ in their protein content. We found that whereas aggresomes generated in cells expressing mutant huntingtin or mutant tau, or co-expressing synphilin-1 and alpha-synuclein, are amenable to clearance by autophagy, those produced in AIMP2 (p38)- or mutant desmin-expressing cells are apparently resistant to autophagic clearance. Notably, AIMP2 (p38)- and desmin-positive inclusions fail to recruit key components of the autophagic/lysosomal system. However, by altering the composition of inclusions, 'autophagy-resistant' aggresomes could be rendered 'autophagy-susceptible'. Taken together, our results demonstrate that not all aggresomes are efficiently primed for autophagic clearance and highlight a certain degree of selectivity for the supposedly non-discriminative pathway.