Zentrum für Molekulare Biologie der Universität Heidelberg, Deutsches Krebsforschungszentrum, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
J Cell Biol. 2011 Nov 14;195(4):617-29. doi: 10.1083/jcb.201106037. Epub 2011 Nov 7.
The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors.
细胞内蛋白质的聚集是一个具有细胞保护功能的有序过程。在酿酒酵母中，聚集的蛋白质被空间隔离到核周或外周位置，这些位置针对不同的折叠和降解质量控制途径。驱动这些错误折叠蛋白质聚集到这些位置的细胞机制尚不清楚。在本文中，我们表明，酵母的两种小热休克蛋白之一，Hsp42，对于生理热应激期间外周聚集的形成是必不可少的。Hsp42 优先定位于外周聚集物，但在核周聚集物中大量缺失，而核周聚集物仍在 hsp42Δ 细胞中形成。将 Hsp42 的氨基末端结构域转移到不参与聚集物分类的 Hsp26 上，使 Hsp26 能够替代 Hsp42 的功能。我们的数据表明，Hsp42 通过其氨基末端结构域与错误折叠的蛋白质共同聚集，并可能将这些复合物与进一步的分拣因子连接起来。
