TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER–Golgi intermediate compartments

Michael G. Hanna, Samuel Block, E. B. Frankel, Feng Hou, Adam Johnson, Lin Yuan, Gavin Knight, James J. Moresco, John R. Yates, Randolph Ashton, Randy Schekman, Yufeng Tong, Anjon Audhya

Research output: Contribution to journalArticle

18 Scopus citations


The conserved coat protein complex II (COPII) mediates the initial steps of secretory protein trafficking by assembling onto subdomains of the endoplasmic reticulum (ER) in two layers to generate cargo-laden transport carriers that ultimately fuse with an adjacent ER–Golgi intermediate compartment (ERGIC). Here, we demonstrate that Trk-fused gene (TFG) binds directly to the inner layer of the COPII coat. Specifically, the TFG C terminus interacts with Sec23 through a shared interface with the outer COPII coat and the cargo receptor Tango1/cTAGE5. Our findings indicate that TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and ultimately promotes outer coat dissociation. Additionally, we demonstrate that TFG tethers vesicles harboring the inner COPII coat, which contributes to their clustering between the ER and ERGIC in cells. Together, our studies define a mechanism by which COPII transport carriers are retained locally at the ER/ERGIC interface after outer coat disassembly, which is a prerequisite for fusion with ERGIC membranes.

Original languageEnglish (US)
Pages (from-to)E7707-E7716
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
Publication statusPublished - Sep 12 2017
Externally publishedYes



  • Coat disassembly
  • Endoplasmic reticulum
  • Tether
  • Trk-fused gene

ASJC Scopus subject areas

  • General

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