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

The Plant Cell
Urszula KaniaJiři Friml

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 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 o...Continue Reading

Citations

Apr 24, 2019·Nature Chemical Biology·Wim DejongheEugenia Russinova
May 16, 2019·Journal of Experimental Botany·Marcin Luzarowski, Aleksandra Skirycz
Aug 7, 2020·International Journal of Molecular Sciences·Zhenzhen ZhaoYe Xia
Mar 19, 2021·Plant Physiology·Madhumitha NarasimhanJiří Friml
Sep 30, 2021·The Plant Cell·Leia ColinYvon Jaillais

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