A Case for Sec61 Channel Involvement in ERAD

Proteins that misfold in the endoplasmic reticulum (ER) need to be transported back to the cytosol for degradation by proteasomes, a process known as ER-associated degradation (ERAD). The first candidate discussed as a retrograde protein transport conduit was the Sec61 channel which is responsible for secretory protein transport into the ER during biogenesis. The Sec61 channel binds the proteasome 19S regulatory particle which can extract an ERAD substrate from the ER. Nevertheless its role as a general export channel has been dismissed, and Hrd1 and Der1 have been proposed as alternatives. The discovery of export-specific sec61 mutants and of mammalian ERAD substrates whose export is dependent on the 19S regulatory particle suggest that dismissal of a role of Sec61 in export may have been premature.