title: Inhibition of cargo export at ER exit sites and the trans-Golgi network by the secretion inhibitor FLI-06.
abstract: Export out of the endoplasmic reticulum (ER) involves the Sar1 and COPII machinery acting at ER exit sites (ERES). Whether and how cargo proteins are recruited upstream of Sar1 and COPII is unclear. Two models are conceivable, a recruitment model where cargo is actively transported through a transport factor and handed over to the Sar1 and COPII machinery in ERES, and a capture model, where cargo freely diffuses into ERES where it is captured by the Sar1 and COPII machinery. Using the novel secretion inhibitor FLI-06, we show that recruitment of the cargo VSVG to ERES is an active process upstream of Sar1 and COPII. Applying FLI-06 before concentration of VSVG in ERES completely abolishes its recruitment. In contrast, applying FLI-06 after VSVG concentration in ERES does not lead to dispersal of the concentrated VSVG, arguing that it inhibits recruitment to ERES as opposed to capture in ERES. FLI-06 also inhibits export out of the trans-Golgi network (TGN), suggesting that similar mechanisms might orchestrate cargo selection and concentration at the ER and TGN. FLI-06 does not inhibit autophagosome biogenesis and the ER-peroxisomal transport route, suggesting that these rely on different mechanisms.
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Yoji
authors: Y
authors: Yonemura
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Xiaolin
authors: X
authors: Li
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Katja
authors: K
authors: Müller
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Andreas
authors: A
authors: Krämer
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Paul
authors: 0000-0001-9032-4583
authors: P
authors: Atigbire
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Torben
authors: T
authors: Mentrup
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Talitha
authors: T
authors: Feuerhake
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Torsten
authors: T
authors: Kroll
authors: Pathology Department, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors: Olga
authors: O
authors: Shomron
authors: Lehrstuhl für organische Chemie I, Friedrich-Schiller Universität, Jena 07743, Germany.
authors: Richard
authors: R
authors: Nohl
authors: Lehrstuhl für organische Chemie I, Friedrich-Schiller Universität, Jena 07743, Germany.
authors: Hans-Dieter
authors: HD
authors: Arndt
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Christian
authors: C
authors: Hoischen
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
authors: Peter
authors: P
authors: Hemmerich
authors: Pathology Department, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel koty@post.tau.ac.il ckaether@fli-leibniz.de.
authors: Koret
authors: K
authors: Hirschberg
authors: Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany koty@post.tau.ac.il ckaether@fli-leibniz.de.
authors: Christoph
authors: 0000-0002-6874-2276
authors: C
authors: Kaether
mesh_terms: D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D017510:Protein Folding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011804:Quinolines; C000621625:cyclohexyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
keywords: COP II; ER exit sites; ER export; Secretion; Secretory pathway; Trans-Golgi network; VSVG