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Clusters of bioactive compounds target dynamic endomembrane networks in vivo

Georgia Drakakaki, Stephanie Robert UGent, Anna Maria Szatmari UGent, Michelle Q Brown, Shingo Nagawa, Daniël Van Damme UGent, Marilyn Leonard, Zhenbiao Yang, Thomas Girke and Sandra L Schmid, et al. (2011) PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 108(43). p.17850-17855
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
endosidin, endosome, chemical genomics, high content screen
journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Proc. Natl. Acad. Sci. USA
volume
108
issue
43
pages
17850 - 17855
Web of Science type
Article
Web of Science id
000296378100061
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
9.681 (2011)
JCR rank
3/54 (2011)
JCR quartile
1 (2011)
ISSN
0027-8424
DOI
10.1073/pnas.1108581108
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1954343
handle
http://hdl.handle.net/1854/LU-1954343
date created
2011-11-25 16:51:55
date last changed
2011-11-29 15:09:14
@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, Dani{\"e}l 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},
  keyword      = {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},
}

Chicago
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.
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.
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.
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.