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Clusters of bioactive compounds target dynamic endomembrane networks in vivo

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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.
Keywords
endosidin, endosome, chemical genomics, high content screen

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MLA
Drakakaki, Georgia, Stephanie Robert, Anna Maria Szatmari, et al. “Clusters of Bioactive Compounds Target Dynamic Endomembrane Networks in Vivo.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.43 (2011): 17850–17855. Print.
APA
Drakakaki, G., Robert, S., Szatmari, A. M., Brown, M. Q., Nagawa, S., Van Damme, D., Leonard, M., et al. (2011). Clusters of bioactive compounds target dynamic endomembrane networks in vivo. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(43), 17850–17855.
Chicago author-date
Drakakaki, Georgia, Stephanie Robert, Anna Maria Szatmari, Michelle Q Brown, Shingo Nagawa, Daniël Van Damme, Marilyn Leonard, et al. 2011. “Clusters of Bioactive Compounds Target Dynamic Endomembrane Networks in Vivo.” Proceedings of the National Academy of Sciences of the United States of America 108 (43): 17850–17855.
Chicago author-date (all authors)
Drakakaki, Georgia, Stephanie Robert, Anna Maria Szatmari, Michelle Q Brown, Shingo Nagawa, Daniël Van Damme, Marilyn Leonard, Zhenbiao Yang, Thomas Girke, Sandra L Schmid, Eugenia Russinova, Jiri Friml, Natasha V Raikhel, and Glenn R Hicks. 2011. “Clusters of Bioactive Compounds Target Dynamic Endomembrane Networks in Vivo.” Proceedings of the National Academy of Sciences of the United States of America 108 (43): 17850–17855.
Vancouver
1.
Drakakaki G, Robert S, Szatmari AM, Brown MQ, Nagawa S, Van Damme D, et al. Clusters of bioactive compounds target dynamic endomembrane networks in vivo. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2011;108(43):17850–5.
IEEE
[1]
G. Drakakaki et al., “Clusters of bioactive compounds target dynamic endomembrane networks in vivo,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 108, no. 43, pp. 17850–17855, 2011.
@article{1954343,
  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.},
  author       = {Drakakaki, Georgia and Robert, Stephanie and Szatmari, Anna Maria and Brown, Michelle Q and Nagawa, Shingo and Van Damme, Daniël and Leonard, Marilyn and Yang, Zhenbiao and Girke, Thomas and Schmid, Sandra L and Russinova, Eugenia and Friml, Jiri and Raikhel, Natasha V and Hicks, Glenn R},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {endosidin,endosome,chemical genomics,high content screen},
  language     = {eng},
  number       = {43},
  pages        = {17850--17855},
  title        = {Clusters of bioactive compounds target dynamic endomembrane networks in vivo},
  url          = {http://dx.doi.org/10.1073/pnas.1108581108},
  volume       = {108},
  year         = {2011},
}

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