Abstract
In mammalian cells, cargo-laden secretory vesicles leave the endoplasmic reticulum (ER) en route to ER-Golgi intermediate compartments (ERGIC) in a manner dependent on the COPII coat complex. We report here that COPII-coated transport carriers traverse a submicron, TFG (Trk-fused gene)-enriched zone at the ER/ERGIC interface. The architecture of TFG complexes as determined by three-dimensional electron microscopy reveals the formation of flexible, octameric cup-like structures, which are able to self-associate to generate larger polymers in vitro. In cells, loss of TFG function dramatically slows protein export from the ER and results in the accumulation of COPII-coated carriers throughout the cytoplasm. Additionally, the tight association between ER and ERGIC membranes is lost in the absence of TFG. We propose that TFG functions at the ER/ERGIC interface to locally concentrate COPII-coated transport carriers and link exit sites on the ER to ERGIC membranes. Our findings provide a new mechanism by which COPII-coated carriers are retained near their site of formation to facilitate rapid fusion with neighboring ERGIC membranes upon uncoating, thereby promoting interorganellar cargo transport.
Keywords:
COPII vesicle transport; intrinsic disorder; secretion; single particle electron microscopy.