The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue The Plant cell Année : 2018

The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes

Urszula Kania
  • Fonction : Auteur
Tomasz Nodzyński
  • Fonction : Auteur
Qing Lu
  • Fonction : Auteur
Glenn Hicks
  • Fonction : Auteur
Wim Nerinckx
  • Fonction : Auteur
Kiril Mishev
  • Fonction : Auteur
Riet de Rycke
  • Fonction : Auteur
Peter Grones
  • Fonction : Auteur
Stéphanie Robert
  • Fonction : Auteur
  • PersonId : 837011
Eugenia Russinova
Jiří Friml

Résumé

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 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.

Dates et versions

hal-02363300 , version 1 (19-11-2019)

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Citer

Urszula Kania, Tomasz Nodzyński, Qing Lu, Glenn Hicks, Wim Nerinckx, et al.. The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes. The Plant cell, 2018, 30 (10), pp.2553-2572. ⟨10.1105/tpc.18.00127⟩. ⟨hal-02363300⟩
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