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| Content Provider | PubMed Central |
|---|---|
| Author | Zouhar, Jan Hicks, Glenn R. Raikhel, Natasha V. |
| Copyright Year | 2004 |
| Abstract | Chemical genomics is an interdisciplinary approach that unites the power of chemical screens and genomics strategies to dissect biological processes such as endomembrane trafficking. We have taken advantage of the evolutionary conservation between plants and Saccharomyces cerevisiae to identify such chemicals. Using S. cerevisiae, we screened a library of diverse chemical structures for compounds that induce the secretion of carboxypeptidase Y, which is normally targeted to the vacuole. Among 4,800 chemicals screened, 14 compounds, termed sorting inhibitors (Sortins), were identified that stimulated secretion in yeast. In Arabidopsis seedlings, application of Sortin1 and -2 led to reversible defects in vacuole biogenesis and root development. Sortin1 was found to redirect the vacuolar destination of plant carboxypeptidase Y and other proteins in Arabidopsis suspension cells and cause these proteins to be secreted. Sortin1 treatment of whole Arabidopsis seedlings also resulted in carboxypeptidase Y secretion, indicating that the drug has a similar mode of action in cells and intact plants. We have demonstrated that screening of a simple eukaryote, in which vacuolar biogenesis is not essential, can be a powerful tool to find chemicals that interfere with vacuolar delivery of proteins in plants, where vacuole biogenesis is essential. Our studies were done by using a sublethal dose of Sortin1, demonstrating the powerful ability of the chemical to control the induced phenotype in a manner that would be difficult to achieve using conventional genetics. |
| Related Links | http://dx.doi.org/10.1073/pnas.0402121101 |
| Ending Page | 9501 |
| Page Count | 5 |
| Starting Page | 9497 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-06-22 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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