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The inhibitor endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with subcellular trafficking in eukaryotes

Urszula Kania (UGent) , Tomasz Nodzyński (UGent) , Qing Lu (UGent) , Glenn R. Hicks, Wim Nerinckx (UGent) , Kiril Mishev (UGent) , Francois Peurois, Jacqueline Cherfils, Riet De Rycke (UGent) , Peter Grones, et al.
(2018) PLANT CELL. 30(10). p.2553-2572
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Abstract
The trafficking of subcellular cargos in eukaryotic cells crucially depends on vesicle budding, a process mediated by ARFGEFs (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 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 (Saccharomyces 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.
Keywords
GUANINE-NUCLEOTIDE-EXCHANGE, ADP-RIBOSYLATION FACTOR-1, AUXIN EFFLUX CARRIER, TRANS-GOLGI NETWORK, ENDOPLASMIC-RETICULUM, YEAST GOLGI, ARABIDOPSIS-THALIANA, ROOT GRAVITROPISM, BREFELDIN-A, INDUCED HAPLOINSUFFICIENCY

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Citation

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MLA
Kania, Urszula, et al. “The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes.” PLANT CELL, vol. 30, no. 10, 2018, pp. 2553–72, doi:10.1105/tpc.18.00127.
APA
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 subcellular trafficking in eukaryotes. PLANT CELL, 30(10), 2553–2572. https://doi.org/10.1105/tpc.18.00127
Chicago author-date
Kania, Urszula, Tomasz Nodzyński, Qing Lu, Glenn R. Hicks, Wim Nerinckx, Kiril Mishev, Francois Peurois, et al. 2018. “The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes.” PLANT CELL 30 (10): 2553–72. https://doi.org/10.1105/tpc.18.00127.
Chicago author-date (all authors)
Kania, Urszula, Tomasz Nodzyński, Qing Lu, Glenn R. Hicks, Wim Nerinckx, Kiril Mishev, Francois Peurois, Jacqueline Cherfils, Riet De Rycke, Peter Grones, Stephanie Robert, Eugenia Russinova, and Jiri Friml. 2018. “The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes.” PLANT CELL 30 (10): 2553–2572. doi:10.1105/tpc.18.00127.
Vancouver
1.
Kania U, Nodzyński T, Lu Q, Hicks GR, Nerinckx W, Mishev K, et al. The inhibitor endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with subcellular trafficking in eukaryotes. PLANT CELL. 2018;30(10):2553–72.
IEEE
[1]
U. Kania et al., “The inhibitor endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with subcellular trafficking in eukaryotes,” PLANT CELL, vol. 30, no. 10, pp. 2553–2572, 2018.
@article{8583919,
  abstract     = {{The trafficking of subcellular cargos in eukaryotic cells crucially depends on vesicle budding, a process mediated by ARFGEFs (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 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 (Saccharomyces 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.}},
  author       = {{Kania, Urszula and Nodzyński, Tomasz and Lu, Qing and Hicks, Glenn R. and Nerinckx, Wim and Mishev, Kiril and Peurois, Francois and Cherfils, Jacqueline and De Rycke, Riet and Grones, Peter and Robert, Stephanie and Russinova, Eugenia and Friml, Jiri}},
  issn         = {{1040-4651}},
  journal      = {{PLANT CELL}},
  keywords     = {{GUANINE-NUCLEOTIDE-EXCHANGE,ADP-RIBOSYLATION FACTOR-1,AUXIN EFFLUX CARRIER,TRANS-GOLGI NETWORK,ENDOPLASMIC-RETICULUM,YEAST GOLGI,ARABIDOPSIS-THALIANA,ROOT GRAVITROPISM,BREFELDIN-A,INDUCED HAPLOINSUFFICIENCY}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2553--2572}},
  title        = {{The inhibitor endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors and interferes with subcellular trafficking in eukaryotes}},
  url          = {{http://dx.doi.org/10.1105/tpc.18.00127}},
  volume       = {{30}},
  year         = {{2018}},
}
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