Fidelity of Cargo Sorting

Vesicles that carry proteins from the ER to the Golgi are encapsulated by a set of coat proteins known as COPII. Two different processes, known as quality control mechanisms, select the correct subset of ER proteins to be admitted into COPII vesicles. The first process retains incompletely folded proteins within the ER by an unknown mechanism. We are currently devising genetic screens to identify mutations that allow inappropriate transport of incompletely folded proteins for genes required for proper protein retention. The second process involves targeting signals that allow the COPII coat proteins to selectively incorporate signal-bearing proteins into budding transport vesicles. The plasma membrane proton-ATPase (Pma1p) is one of the most abundant yeast membrane proteins and requires a number of specialized proteins for its correct exit from the ER. We identified, and are studying a gene called EXP1, which encodes a small membrane protein required for efficient transport of Pma1p. Exp1p cycles between the ER and Golgi and binds to the COPII subunit Sec24p, indicating that Exp1p acts as an adaptor for efficient packaging of Pma1p into COPII vesicle buds.