downregulation of the hsp90 system causes defects in muscle cells of caenorhabditis elegansdownregulation一半的系统导致肌肉细胞缺陷的线虫.pdfVIP

Downregulation of the Hsp90 System Causes Defects in Muscle Cells of Caenorhabditis Elegans Andreas M. Gaiser., Christoph J. O. Kaiser., Veronika Haslbeck., Klaus Richter* ¨ ¨ ¨ Department of Chemistry and Center for Integrated Protein Science Munich (CIPSM) and Technische Universitat Munchen, Munchen, Germany Abstract The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21) has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. Whil