ASSEMBLY, SORTING, AND EXIT OF OLIGOMERIC PROTEINS FROM THE ENDOPLASMIC-RETICULUM

The endoplasmic reticulum (ER) uses various mechanisms to ensure that only properly folded proteins enter the secretory pathway. For protein s that oligomerize in the ER, the proper tertiary and quaternary struc tures must be achieved before their release, Although some proteins fo ld before oligomerization, others initiate oligomerization cotranslati onally. Here, we discuss these different strategies and some of the un ique problems they present for the ER quality control system, One mech anism used by the ER is thiol retention. Thiol retention operates by m onitoring the redox state of specific cysteine residue(s) and was disc overed in studies on the assembly of IgM, a complex oligomeric glycopr otein. This system is also involved in retaining other unassembled pro teins in the ER. Mutations that result in uneven numbers of cysteine r esidues can subject yet other proteins to thiol retention, altering th eir oligomerization status and function. The implications of these res ults on the effects of thiol retention on protein function and cell fa te are discussed. (C) 1998 John Wiley & Sons, Inc.