期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 20, 页码 3868-3877出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.186163
关键词
VSVG; ER exit sites; ER export; COP II; Secretory pathway; Secretion; Trans-Golgi network
类别
资金
- Deutsche Forschungsgemeinschaft [KA1751/4-1]
- Japan Society for the Promotion of Science
- Israel Science Foundation [1533/12]
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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