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

Misfolded secretory and transmembrane proteins are retained in the endoplasmic reticulum (ER) and subsequently degraded. Degradation is primarily mediated by cytosolic proteasomes and thus requires retrograde transport out of the ER back to the cytosol. The available evidence suggests that the protein-conducting channel formed by the Sec61 complex is responsible for both forward and retrograde transport of proteins across the ER membrane. For transmembrane proteins, retrograde transport can be viewed as a reversal of integration of membrane proteins into the ER membrane. Retrograde transport of soluble proteins through the Sec61 channel after signal-peptide cleavage, however, must be mechanistically distinct from signal-peptide-mediated import into the ER through the same channel.

[1]  T. Rapoport,et al.  Sec6l-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction , 1996, Nature.

[2]  T. Rapoport,et al.  BiP Acts as a Molecular Ratchet during Posttranslational Transport of Prepro-α Factor across the ER Membrane , 1999, Cell.

[3]  B. Wilkinson,et al.  Molecular architecture of the ER translocase probed by chemical crosslinking of Sss1p to complementary fragments of Sec61p , 1997, The EMBO journal.

[4]  A. Helenius,et al.  Quality control in the secretory pathway. , 1995, Current opinion in cell biology.

[5]  J. Brodsky,et al.  ER-associated and proteasomemediated protein degradation: how two topologically restricted events came together. , 1997, Trends in cell biology.

[6]  R. Schekman,et al.  Binding of Secretory Precursor Polypeptides to a Translocon Subcomplex Is Regulated by BiP , 1997, Cell.

[7]  H. Ploegh,et al.  The α Chain of the T Cell Antigen Receptor Is Degraded in the Cytosol , 1997 .

[8]  J. Riordan,et al.  Multiple proteolytic systems, including the proteasome, contribute to CFTR processing , 1995, Cell.

[9]  D. Lomas,et al.  A Kinetic Mechanism for the Polymerization of α1-Antitrypsin* , 1999, The Journal of Biological Chemistry.

[10]  R. Plemper,et al.  Re‐entering the translocon from the lumenal side of the endoplasmic reticulum. Studies on mutated carboxypeptidase yscY species , 1999, FEBS letters.

[11]  T. Biederer,et al.  Role of Cue1p in ubiquitination and degradation at the ER surface. , 1997, Science.

[12]  T. Rapoport,et al.  Signal Sequence Processing in Rough Microsomes (*) , 1995, The Journal of Biological Chemistry.

[13]  W. Skach,et al.  Evidence That Endoplasmic Reticulum (ER)-associated Degradation of Cystic Fibrosis Transmembrane Conductance Regulator Is Linked to Retrograde Translocation from the ER Membrane* , 1999, The Journal of Biological Chemistry.

[14]  Tom A. Rapoport,et al.  Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p , 1995, Cell.

[15]  B. Jungnickel,et al.  A posttargeting signal sequence recognition event in the endoplasmic reticulum membrane , 1995, Cell.

[16]  L. Hendershot,et al.  BiP Maintains the Permeability Barrier of the ER Membrane by Sealing the Lumenal End of the Translocon Pore before and Early in Translocation , 1998, Cell.

[17]  T. Imamura,et al.  Involvement of Heat Shock Protein 90 in the Degradation of Mutant Insulin Receptors by the Proteasome* , 1998, The Journal of Biological Chemistry.

[18]  O. Gruss,et al.  Phosphorylation of components of the ER translocation site. , 1999, European journal of biochemistry.

[19]  R. Klausner,et al.  Protein degradation in the endoplasmic reticulum , 1990, Cell.

[20]  M. Makarow,et al.  Dissection of the translocation and chaperoning functions of yeast BiP/Kar2p in vivo. , 1998, Journal of cell science.

[21]  S. Ōmura,et al.  Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes , 1998, The Journal of experimental medicine.

[22]  R. Schekman,et al.  Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubunit complex , 1991, Nature.

[23]  P. A. Peterson,et al.  In Vivo Assembly of the Proteasomal Complexes, Implications for Antigen Processing (*) , 1995, The Journal of Biological Chemistry.

[24]  R. Plemper,et al.  Genetic interactions of Hrd3p and Der3p/Hrd1p with Sec61p suggest a retro-translocation complex mediating protein transport for ER degradation. , 1999, Journal of cell science.

[25]  C. Milstein,et al.  Russell bodies: a general response of secretory cells to synthesis of a mutant immunoglobulin which can neither exit from, nor be degraded in, the endoplasmic reticulum , 1991, The Journal of cell biology.

[26]  J. Brodsky,et al.  Proteasome-dependent endoplasmic reticulum-associated protein degradation: An unconventional route to a familiar fate , 1996 .

[27]  T. Rapoport,et al.  The β Subunit of the Sec61 Complex Facilitates Cotranslational Protein Transport and Interacts with the Signal Peptidase during Translocation , 1998, The Journal of cell biology.

[28]  R. Schekman,et al.  Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation , 1997, The EMBO journal.

[29]  J. Rine,et al.  Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. , 1996, Molecular biology of the cell.

[30]  M. Bogyo,et al.  The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the Cytosol , 1996, Cell.

[31]  B. J. Roberts.  Evidence of Proteasome-mediated Cytochrome P-450 Degradation* , 1997, The Journal of Biological Chemistry.

[32]  M. Aebi,et al.  Degradation of Misfolded Endoplasmic Reticulum Glycoproteins in Saccharomyces cerevisiae Is Determined by a Specific Oligosaccharide Structure , 1998, The Journal of cell biology.

[33]  S. Jentsch,et al.  Role of the proteasome in membrane extraction of a short‐lived ER‐transmembrane protein , 1998, The EMBO journal.

[34]  M. Knop,et al.  Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. , 1996, The EMBO journal.

[35]  H. Ploegh,et al.  Dislocation of Type I Membrane Proteins from the ER to the Cytosol Is Sensitive to Changes in Redox Potential , 1998, The Journal of cell biology.

[36]  K. Kitajima,et al.  Peptides Glycosylated in the Endoplasmic Reticulum of Yeast Are Subsequently Deglycosylated by a Soluble Peptide: N-Glycanase Activity* , 1998, The Journal of Biological Chemistry.

[37]  T. Rapoport,et al.  A second trimeric complex containing homologs of the Sec61p complex functions in protein transport across the ER membrane of S. cerevisiae. , 1996, The EMBO journal.

[38]  B. Wilkinson,et al.  Signal Sequence Recognition in Posttranslational Protein Transport across the Yeast ER Membrane , 1998, Cell.

[39]  J. Brodsky,et al.  Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP , 1996, The Journal of cell biology.

[40]  M. de Virgilio,et al.  Ubiquitination Is Required for the Retro-translocation of a Short-lived Luminal Endoplasmic Reticulum Glycoprotein to the Cytosol for Degradation by the Proteasome* , 1998, The Journal of Biological Chemistry.

[41]  M. Knop,et al.  N‐glycosylation affects endoplasmic reticulum degradation of a mutated derivative of carboxypeptidase yscY in yeast , 1996, Yeast.

[42]  H. Riezman.  The Ins and Outs of Protein Translocation , 1997, Science.

[43]  R. Schekman,et al.  Sec61p serves multiple roles in secretory precursor binding and translocation into the endoplasmic reticulum membrane. , 1998, Molecular biology of the cell.

[44]  P. De Camilli,et al.  Yeast protein translocation complex: Isolation of two genes SEB1 and SEB2 encoding proteins homologous to the Sec61β subunit , 1996, Yeast.

[45]  T. Biederer,et al.  Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin‐proteasome pathway. , 1996, The EMBO journal.

[46]  D. Wolf,et al.  ER Degradation of a Misfolded Luminal Protein by the Cytosolic Ubiquitin-Proteasome Pathway , 1996, Science.

[47]  A. Helenius,et al.  Interactions between Newly Synthesized Glycoproteins, Calnexin and a Network of Resident Chaperones in the Endoplasmic Reticulum , 1997, The Journal of cell biology.

[48]  J. Brodsky,et al.  ER protein quality control and proteasome-mediated protein degradation. , 1999, Seminars in cell & developmental biology.

[49]  R. Plemper,et al.  Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. , 1998, Molecular biology of the cell.

[50]  J. Brodsky,et al.  The Requirement for Molecular Chaperones during Endoplasmic Reticulum-associated Protein Degradation Demonstrates That Protein Export and Import Are Mechanistically Distinct* , 1999, The Journal of Biological Chemistry.

[51]  J. Riordan,et al.  Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome , 1998, The EMBO journal.

[52]  P. Kloetzel,et al.  Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope–ER network in yeast , 1998, The EMBO journal.

[53]  J. Winther,et al.  Competition between folding and glycosylation in the endoplasmic reticulum. , 1996, The EMBO journal.

[54]  D. Feldheim,et al.  Sec72p contributes to the selective recognition of signal peptides by the secretory polypeptide translocation complex , 1994, The Journal of cell biology.

[55]  D. Andrews,et al.  The Cotranslational Integration of Membrane Proteins into the Phospholipid Bilayer Is a Multistep Process , 1996, Cell.

[56]  T. Rapoport,et al.  Protein Translocation: Tunnel Vision , 1998, Cell.

[57]  K. Kuchler,et al.  Endoplasmic Reticulum Degradation of a Mutated ATP-binding Cassette Transporter Pdr5 Proceeds in a Concerted Action of Sec61 and the Proteasome* , 1998, The Journal of Biological Chemistry.

[58]  S. Sather,et al.  Degradation of HMG-CoA Reductase in Vitro , 1998, The Journal of Biological Chemistry.

[59]  R. Schekman,et al.  Sec61p and BiP directly facilitate polypeptide translocation into the ER , 1992, Cell.

[60]  R. Schekman,et al.  The Lumenal Domain of Sec63p Stimulates the ATPase Activity of BiP and Mediates BiP Recruitment to the Translocon in Saccharomyces cerevisiae , 1997, The Journal of cell biology.

[61]  R. Schekman,et al.  SSS1 encodes a stabilizing component of the Sec61 subcomplex of the yeast protein translocation apparatus. , 1994, The Journal of biological chemistry.

[62]  B. Wilkinson,et al.  Determination of the Transmembrane Topology of Yeast Sec61p, an Essential Component of the Endoplasmic Reticulum Translocation Complex* , 1996, The Journal of Biological Chemistry.

[63]  Satoshi Omura,et al.  Degradation of CFTR by the ubiquitin-proteasome pathway , 1995, Cell.

[64]  B. Jungnickel,et al.  Oligomeric Rings of the Sec61p Complex Induced by Ligands Required for Protein Translocation , 1996, Cell.

[65]  K D Wittrup,et al.  Protein Folding Stability Can Determine the Efficiency of Escape from Endoplasmic Reticulum Quality Control* , 1998, The Journal of Biological Chemistry.

[66]  R. Plemper,et al.  Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation , 1997, Nature.