---
_id: '147'
abstract:
- lang: eng
text: 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.
acknowledgement: We thank Gerd Jürgens, Sandra Richter, and Sheng Yang He for providing
antibodies; Maciek Adamowski, Fernando Aniento, Sebastian Bednarek, Nico Callewaert,
Matyás Fendrych, Elena Feraru, and Mugurel I. Feraru for helpful suggestions; Siamsa
Doyle for critical reading of the manuscript and helpful comments and suggestions;
and Stephanie Smith and Martine De Cock for help in editing and language corrections.
We acknowledge the core facility Cellular Imaging of CEITEC supported by the Czech-BioImaging
large RI project (LM2015062 funded by MEYS CR) for their support with obtaining
scientific data presented in this article. Plant Sciences Core Facility of CEITEC
Masaryk University is gratefully acknowledged for obtaining part of the scientific
data presented in this article. We acknowledge support from the Fondation pour la
Recherche Médicale and from the Institut National du Cancer (J.C.). The research
leading to these results was funded by the European Research Council under the European
Union's 7th Framework Program (FP7/2007-2013)/ERC grant agreement numbers 282300
and 742985 and the Czech Science Foundation GAČR (GA18-26981S; J.F.); Ministry of
Education, Youth, and Sports/MEYS of the Czech Republic under the Project CEITEC
2020 (LQ1601; T.N.); the China Science Council for a predoctoral fellowship (Q.L.);
a joint research project within the framework of cooperation between the Research
Foundation-Flanders and the Bulgarian Academy of Sciences (VS.025.13N; K.M. and
E.R.); Vetenskapsrådet and Vinnova (Verket för Innovationssystem; S.R.), Knut och
Alice Wallenbergs Stiftelse via “Shapesystem” Grant 2012.0050 (S.R.), Kempe stiftelserna
(P.G.), Tryggers CTS410 (P.G.).
article_processing_charge: No
article_type: original
author:
- first_name: Urszula
full_name: Kania, Urszula
id: 4AE5C486-F248-11E8-B48F-1D18A9856A87
last_name: Kania
- first_name: Tomasz
full_name: Nodzyński, Tomasz
last_name: Nodzyński
- first_name: Qing
full_name: Lu, Qing
last_name: Lu
- first_name: Glenn R
full_name: Hicks, Glenn R
last_name: Hicks
- first_name: Wim
full_name: Nerinckx, Wim
last_name: Nerinckx
- first_name: Kiril
full_name: Mishev, Kiril
last_name: Mishev
- first_name: Francois
full_name: Peurois, Francois
last_name: Peurois
- first_name: Jacqueline
full_name: Cherfils, Jacqueline
last_name: Cherfils
- first_name: Rycke Riet Maria
full_name: De, Rycke Riet Maria
last_name: De
- first_name: Peter
full_name: Grones, Peter
id: 399876EC-F248-11E8-B48F-1D18A9856A87
last_name: Grones
- first_name: Stéphanie
full_name: Robert, Stéphanie
last_name: Robert
- first_name: Eugenia
full_name: Russinova, Eugenia
last_name: Russinova
- first_name: Jirí
full_name: Friml, Jirí
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: 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
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 sub cellular trafficking in eukaryotes. The
Plant Cell. Oxford University Press. https://doi.org/10.1105/tpc.18.00127
chicago: 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. Oxford University Press, 2018. https://doi.org/10.1105/tpc.18.00127.
ieee: 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. Oxford University Press, pp. 2553–2572,
2018.
ista: 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.
mla: 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, Oxford University Press, 2018, pp. 2553–72,
doi:10.1105/tpc.18.00127.
short: 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.
date_created: 2018-12-11T11:44:52Z
date_published: 2018-11-12T00:00:00Z
date_updated: 2023-09-19T10:09:12Z
day: '12'
department:
- _id: JiFr
doi: 10.1105/tpc.18.00127
ec_funded: 1
external_id:
isi:
- '000450000500023'
pmid:
- '30018156'
intvolume: ' 30'
isi: 1
issue: '10'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1105/tpc.18.00127
month: '11'
oa: 1
oa_version: Published Version
page: 2553 - 2572
pmid: 1
project:
- _id: 25716A02-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '282300'
name: Polarity and subcellular dynamics in plants
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
publication: The Plant Cell
publication_identifier:
issn:
- 1040-4651
publication_status: published
publisher: Oxford University Press
publist_id: '7776'
quality_controlled: '1'
scopus_import: '1'
status: public
title: The inhibitor Endosidin 4 targets SEC7 domain-type ARF GTPase exchange factors
and interferes with sub cellular trafficking in eukaryotes
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2018'
...