The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes

U. Kania, T. Nodzyński, Q. Lu, G.R. Hicks, W. Nerinckx, K. Mishev, F. Peurois, J. Cherfils, R.R.M. De, P. Grones, S. Robert, E. Russinova, J. Friml, The Plant Cell 30 (2018) 2553–2572.


Journal Article | Published | English
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Abstract
The trafficking of subcellular cargos in eukaryotic cells crucially depends on vesicle budding, a process mediated by ARF-GEFs (ADP-ribosylation factor guanine nucleotide exchange factors). In plants, ARF-GEFs play essential roles in endocytosis, vacuolar trafficking, recycling, secretion, and polar trafficking. Moreover, they are important for plant development, mainly through controlling the polar subcellular localization of PIN-FORMED (PIN) transporters of the plant hormone auxin. Here, using a chemical genetics screen in Arabidopsis thaliana, we identified Endosidin 4 (ES4), an inhibitor of eukaryotic ARF-GEFs. ES4 acts similarly to and synergistically with the established ARF-GEF inhibitor Brefeldin A and has broad effects on intracellular trafficking, including endocytosis, exocytosis, and vacuolar targeting. Additionally, Arabidopsis and yeast (Sacharomyces cerevisiae) mutants defective in ARF-GEF show altered sensitivity to ES4. ES4 interferes with the activation-based membrane association of the ARF1 GTPases, but not of their mutant variants that are activated independently of ARF-GEF activity. Biochemical approaches and docking simulations confirmed that ES4 specifically targets the SEC7 domain-containing ARF-GEFs. These observations collectively identify ES4 as a chemical tool enabling the study of ARF-GEF-mediated processes, including ARF-GEF-mediated plant development.
Publishing Year
Date Published
2018-11-12
Journal Title
The Plant Cell
Volume
30
Issue
10
Page
2553 - 2572
IST-REx-ID

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Kania U, Nodzyński T, Lu Q, et al. The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes. The Plant Cell. 2018;30(10):2553-2572. doi:10.1105/tpc.18.00127
Kania, U., Nodzyński, T., Lu, Q., Hicks, G. R., Nerinckx, W., Mishev, K., … Friml, J. (2018). The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes. The Plant Cell, 30(10), 2553–2572. https://doi.org/10.1105/tpc.18.00127
Kania, Urszula, Tomasz Nodzyński, Qing Lu, Glenn R Hicks, Wim Nerinckx, Kiril Mishev, Francois Peurois, et al. “The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Sub Cellular Trafficking in Eukaryotes.” The Plant Cell 30, no. 10 (2018): 2553–72. https://doi.org/10.1105/tpc.18.00127.
U. Kania et al., “The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes,” The Plant Cell, vol. 30, no. 10, pp. 2553–2572, 2018.
Kania U, Nodzyński T, Lu Q, Hicks GR, Nerinckx W, Mishev K, Peurois F, Cherfils J, De RRM, Grones P, Robert S, Russinova E, Friml J. 2018. The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with sub cellular trafficking in eukaryotes. The Plant Cell. 30(10), 2553–2572.
Kania, Urszula, et al. “The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Sub Cellular Trafficking in Eukaryotes.” The Plant Cell, vol. 30, no. 10, NLM , 2018, pp. 2553–72, doi:10.1105/tpc.18.00127.

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PMID: 30018156
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