Cargo can modulate COPII vesicle formation from the endoplasmic reticulum

The COPII coat complex found on endoplasmic reticulum (ER)-derived vesicles plays a critical role in cargo selection. We now address the potential rol e of biosynthetic cargo in modulating COPII coat assembly and vesicle buddi ng. The ER accumulation of vesicular stomatitis glycoprotein (VSV-G), a tra nsmembrane protein, or the soluble PiZ variant of alpha 1-antitrypsin, redu ced levels of general COPII vesicle formation in vivo. Consistent with this result, conditions that prevent the export of VSV-G; from the ER led to a significant inhibition of general COPII vesicle budding from ER microsomes and the export of an endogenous recycling protein p58 in vitro. In contrast , synchronized export of VSV-G stimulated COPII vesicle budding both in viv o and in vitro. Under conditions where VSV-G is retained in the ER, we find that it can to be recovered in pre-budding complexes containing COPII comp onents. These results suggest that the export of biosynthetic cargo is inte grated with ER functions involved in protein folding and oligomerization. T he ability of biosynthetic cargo to prevent or enhance ER export suggests t hat interactions of cargo with the COPII machinery contribute to the format ion of vesicles budding from the ER.