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@article{1504366,
author = {Kania, U. and Nodzynski, Tomasz and Lu, Q. and Hicks, G.R. and Nerinckx, W. and Mishev, K. and Peurois, F. and Cherfils, J. and De Rycke, R. and Grones, P. and Robert, S. and Russinova, E. and Friml, J.},
article_location = {ROCKVILLE},
article_number = {10},
doi = {http://dx.doi.org/10.1105/tpc.18.00127},
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},
issn = {1040-4651},
journal = {Plant Cell},
title = {The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes},
volume = {30},
year = {2018}
}
TY - JOUR
ID - 1504366
AU - Kania, U. - Nodzynski, Tomasz - Lu, Q. - Hicks, G.R. - Nerinckx, W. - Mishev, K. - Peurois, F. - Cherfils, J. - De Rycke, R. - Grones, P. - Robert, S. - Russinova, E. - Friml, J.
PY - 2018
TI - The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes
JF - Plant Cell
VL - 30
IS - 10
SP - 2553-2572
EP - 2553-2572
PB - AMER SOC PLANT BIOLOGISTS
SN - 10404651
KW - GUANINE-NUCLEOTIDE-EXCHANGE
KW - ADP-RIBOSYLATION FACTOR-1
KW - AUXIN EFFLUX CARRIER
KW - TRANS-GOLGI NETWORK
KW - ENDOPLASMIC-RETICULUM
KW - YEAST GOLGI
KW - ARABIDOPSIS-THALIANA
KW - ROOT GRAVITROPISM
KW - BREFELDIN-A
KW - INDUCED HAPLOINSUFFICIENCY
N2 - 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.
ER -
KANIA, U., Tomasz NODZYNSKI, Q. LU, G.R. HICKS, W. NERINCKX, K. MISHEV, F. PEUROIS, J. CHERFILS, R. DE RYCKE, P. GRONES, S. ROBERT, E. RUSSINOVA and J. FRIML. The Inhibitor Endosidin 4 Targets SEC7 Domain-Type ARF GTPase Exchange Factors and Interferes with Subcellular Trafficking in Eukaryotes. \textit{Plant Cell}. ROCKVILLE: AMER SOC PLANT BIOLOGISTS, 2018, vol.~30, No~10, p.~2553-2572. ISSN~1040-4651. Available from: https://dx.doi.org/10.1105/tpc.18.00127.
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