Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane

Misfolded secretory and transmembrane proteins are retained in the endoplas mic reticulum (ER) ana subsequently degraded. Degradation is primarily medi ated by cytosolic proteasomes and thus requires retrograde transport out of the ER back to the cytosol. The available evidence suggests that the prote in-conducting channel formed by the Sec61 complex is responsible for both f orward and retrograde transport of proteins across the ER membrane. For tra nsmembrane proteins, retrograde and transport can be viewed as a reversal o f integration of membrane proteins into the ER membrane. Retrograde transpo rt of soluble proteins through the Sec61 channel after signal-peptide cleav age, however, must be mechanistically distinct from signal-peptide-mediated import into the ER through the same channel.