Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation

Nature. 1997 Aug 28;388(6645):891-5. doi: 10.1038/42276.


Proteins enter the secretory pathway through the endoplasmic reticulum, which delivers properly folded proteins to their site of action and contains a quality-control system to monitor and prevent abnormal proteins from being delivered. Many of these proteins are degraded by the cytoplasmic proteasome, which requires their retrograde transport to the cytoplasm. Based on a co-immunoprecipitation of major histocompatibility complex (MHC) class I heavy-chain breakdown intermediates with the translocon subunit Sec61p, it was speculated that Sec61p maybe involved in retrograde transport. Here we present functional evidence from genetic studies that Sec61p mediates retrograde transport of a mutated lumenal yeast carboxypeptidase ycsY (CPY*) in vivo. The endoplasmic reticulum lumenal chaperone BiP (Kar2p) and Sec63p, which are also subunits of the import machinery, are involved in export of CPY* to the cytosol. Thus our results demonstrate that retrograde transport of proteins is mediated by a functional translocon. We consider the export of endoplasmic reticulum-localized proteins to the cytosol by the translocon for proteasome degradation to be a general process in eukaryotic cell biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Carboxypeptidases / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins*
  • Ligases / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mutation
  • SEC Translocation Channels
  • Saccharomyces cerevisiae Proteins*
  • Ubiquitin-Conjugating Enzymes*


  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • KAR2 protein, yeast
  • Membrane Proteins
  • Membrane Transport Proteins
  • SEC Translocation Channels
  • SEC63 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • UBC6 protein, S cerevisiae
  • UBE2J1 protein, human
  • UBE2L3 protein, human
  • Ubiquitin-Conjugating Enzymes
  • Carboxypeptidases
  • Ligases