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Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7707-E7716. doi: 10.1073/pnas.1709120114. Epub 2017 Aug 29.

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

Author information

1
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53706.
2
Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
3
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
4
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
5
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706.
6
Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706.
7
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037.
8
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
9
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53706; audhya@wisc.edu.

Abstract

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.

KEYWORDS:

COPII; Trk-fused gene; coat disassembly; endoplasmic reticulum; tether

PMID:
28851831
PMCID:
PMC5604033
DOI:
10.1073/pnas.1709120114
[Indexed for MEDLINE]
Free PMC Article

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