A link between ER tethering and COP-I vesicle uncoating.

The yeast Dsl1p vesicle tethering complex, comprising the three subunits Dsl1p, Dsl3p, and Tip20p, is stably associated with three endoplasmic reticulum-localized Q-SNAREs and is believed to play a central role in the tethering and fusion of Golgi-derived COP-I transport vesicles. Dsl1p also interacts directly with COP-I subunits. We now show that binding of Dsl1p to COP-I subunits involves binding sites identical to those involved in interactions between COP-I subunits that stabilize the COP-I coat. Cells with defects in Dsl/SNARE complex function show massive accumulation of COP-I-coated vesicles in a cluster to which COP-II coat proteins are also recruited. Our results suggest that binding of Dsl/SNARE complex to the COP-I coat complex serves two functions: to mediate vesicle tethering and to assist the uncoating process by blocking domains in COP-I that drive repolymerization and the formation of large COP-I aggregates.