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      Inhibition of cargo export at ER exit sites and the trans-Golgi network by the secretion inhibitor FLI-06.

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          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.

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          Author and article information

          Journal
          J. Cell. Sci.
          Journal of cell science
          The Company of Biologists
          1477-9137
          0021-9533
          October 15 2016
          : 129
          : 20
          Affiliations
          [1 ] Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany.
          [2 ] Pathology Department, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
          [3 ] Lehrstuhl für organische Chemie I, Friedrich-Schiller Universität, Jena 07743, Germany.
          [4 ] Pathology Department, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel koty@post.tau.ac.il ckaether@fli-leibniz.de.
          [5 ] Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, Jena 07745, Germany koty@post.tau.ac.il ckaether@fli-leibniz.de.
          Article
          jcs.186163
          10.1242/jcs.186163
          27587840
          4b94fb74-a8f3-4019-86cb-4b71d21b082e
          History

          ER exit sites,VSVG,Trans-Golgi network,Secretory pathway,Secretion,COP II,ER export

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