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Article Dans Une Revue The Plant cell Année : 2018

Nonselective Chemical Inhibition of Sec7 Domain-Containing ARF GTPase Exchange Factors

Kiril Mishev
  • Fonction : Auteur
Qing Lu
  • Fonction : Auteur
Bram Denoo
  • Fonction : Auteur
Wim Dejonghe
  • Fonction : Auteur
Jan Hullaert
  • Fonction : Auteur
Isha Sharma
  • Fonction : Auteur
Kaija Goodman
  • Fonction : Auteur
Kamila Kalinowska
  • Fonction : Auteur
Le Son Long Nguyen
  • Fonction : Auteur
Dominique Audenaert
Marisa S. Otegui
  • Fonction : Auteur
Erika Isono
  • Fonction : Auteur
Sacco de Vries
  • Fonction : Auteur

Résumé

Small GTP-binding proteins from the ADP-ribosylation factor (ARF) family are important regulators of vesicle formation and cellular trafficking in all eukaryotes. ARF activation is accomplished by a protein family of guanine nucleotide exchange factors (GEFs) that contain a conserved catalytic Sec7 domain. Here, we identified and characterized Secdin, a small-molecule inhibitor of Arabidopsis thaliana ARF-GEFs. Secdin application caused aberrant retention of plasma membrane (PM) proteins in late endosomal compartments, enhanced vacuolar degradation, impaired protein recycling, and delayed secretion and endocytosis. Combined treatments with Secdin and the known ARF-GEF inhibitor Brefeldin A (BFA) prevented the BFA-induced PM stabilization of the ARF-GEF GNOM, impaired its translocation from the Golgi to the trans-Golgi network/early endosomes, and led to the formation of hybrid endomembrane compartments reminiscent of those in ARF-GEF-deficient mutants. Drug affinity-responsive target stability assays revealed that Secdin, unlike BFA, targeted all examined Arabidopsis ARF-GEFs, but that the interaction was probably not mediated by the Sec7 domain because Secdin did not interfere with the Sec7 domain-mediated ARF activation. These results show that Secdin and BFA affect their protein targets through distinct mechanisms, in turn showing the usefulness of Secdin in studies in which ARF-GEF-dependent endomembrane transport cannot be manipulated with BFA.

Dates et versions

hal-02182312 , version 1 (12-07-2019)

Identifiants

Citer

Kiril Mishev, Qing Lu, Bram Denoo, François Peurois, Wim Dejonghe, et al.. Nonselective Chemical Inhibition of Sec7 Domain-Containing ARF GTPase Exchange Factors. The Plant cell, 2018, 30 (10), pp.2573--2593. ⟨10.1105/tpc.18.00145⟩. ⟨hal-02182312⟩
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