Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.chembiol.2010.11.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chemical enhancers of posttranscriptional gene silencing in .
RNA
September 2019
Department of Biology, Swiss Federal Institute of Technology (ETH Zürich), 8092 Zürich, Switzerland.
RNAi mediated by small-interfering RNAs (siRNAs) operates via transcriptional (TGS) and posttranscriptional gene silencing (PTGS). In , TGS relies on DICER-LIKE-3 (DCL3)-dependent 24-nt siRNAs loaded into AGO4-clade ARGONAUTE effector proteins. PTGS operates via DCL4-dependent 21-nt siRNAs loaded into AGO1-clade proteins.
View Article and Find Full Text PDFSynthesis of alkyne-tagged and biotin-tagged Sortin1 as novel photoaffinity probes.
Bioorg Med Chem Lett
May 2018
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-28-16, Naka-cho, Koganei-shi, Tokyo, Japan. Electronic address:
Sortin1 is an inhibitor of vesicular biogenesis and transport, which is shared among eukaryotes and plants with an unknown mode of action. Toward exploration of its target proteins, we developed alkyne as well as biotin conjugated photoaffinity probes derived from Sortin1. Due to the presence of phenylketone moiety, Sortin1 was anticipated to serve as a photoreactive group in a similar manner to a commonly used photoreactive group, benzophenone.
View Article and Find Full Text PDF1H NMR-based metabolomics methods for chemical genomics experiments.
Methods Mol Biol
July 2014
Department of Chemistry, University of California, Riverside, Riverside, CA, USA.
Metabolomics and chemical genomics studies can each provide unique insights into plant biology. Although a variety of analytical techniques can be used for the interrogation of plant systems, nuclear magnetic resonance (NMR) provides unbiased characterization of abundant metabolites. An example methodology is provided for probing the metabolism of Arabidopsis thaliana in a chemical genomics experiment including methods for tissue treatment, tissue collection, metabolite extraction, and methods to minimize variance in biological and technical sample replicates.
View Article and Find Full Text PDFSortin1-hypersensitive mutants link vacuolar-trafficking defects and flavonoid metabolism in Arabidopsis vegetative tissues.
Chem Biol
February 2011
Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California-Riverside, CA 92521, USA.
Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters.
View Article and Find Full Text PDFSorting inhibitors (Sortins): Chemical compounds to study vacuolar sorting in Arabidopsis.
Proc Natl Acad Sci U S A
June 2004
Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California, Riverside, 92521, USA.
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.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!