Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 43, Pages 17850-17855Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1108581108
Keywords
chemical genomics; high content screen; endosidin; endosome
Categories
Funding
- National Science Foundation [MCB-0515963, ABI 0957099, DGE-0504249]
- National Institutes of Health [MH761345]
- Odysseus program
- Vetenskapsrade
- VINNOVA
- Flanders Research Foundation
- University of California
- [G.0065.08]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0957099] Funding Source: National Science Foundation
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Endomembrane trafficking relies on the coordination of a highly complex, dynamic network of intracellular vesicles. Understanding the network will require a dissection of cargo and vesicle dynamics at the cellular level in vivo. This is also a key to establishing a link between vesicular networks and their functional roles in development. We used a high-content intracellular screen to discover small molecules targeting endomembrane trafficking in vivo in a complex eukaryote, Arabidopsis thaliana. Tens of thousands of molecules were prescreened and a selected subset was interrogated against a panel of plasma membrane (PM) and other endomembrane compartment markers to identify molecules that altered vesicle trafficking. The extensive image dataset was transformed by a flexible algorithm into a marker-by-phenotype-by-treatment time matrix and revealed groups of molecules that induced similar subcellular fingerprints (clusters). This matrix provides a platform for a systems view of trafficking. Molecules from distinct clusters presented avenues and enabled an entry point to dissect recycling at the PM, vacuolar sorting, and cell-plate maturation. Bioactivity in human cells indicated the value of the approach to identifying small molecules that are active in diverse organisms for biology and drug discovery.
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