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Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17850-5. doi: 10.1073/pnas.1108581108. Epub 2011 Oct 17.

Clusters of bioactive compounds target dynamic endomembrane networks in vivo.

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  • 1Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA.

Abstract

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.

PMID:
22006339
[PubMed - indexed for MEDLINE]
PMCID:
PMC3203817
Free PMC Article
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