DOI: 10.1091/mbc.e03-10-0765. Endoplasmic Reticulum Quality Control of Unassembled Iron Transporter Depends on Rer1p-mediated Retrieval from the Golgi

Endoplasmic Reticulum Quality Control of Unassembled Iron Transporter Depends on Rer1p-mediated Retrieval from the Golgi

10.1091/mbc.e03-10-0765

Crossref journal-article

American Society for Cell Biology (ASCB)

Molecular Biology of the Cell (1076)

Abstract

Endoplasmic reticulum (ER) quality control is a conserved process by which misfolded or unassembled proteins are selectively retained in the endoplasmic reticulum (ER). Failure in oligomerization of multisubunit membrane proteins is one of the events that triggers ER quality control. The transmembrane domains (TMDs) of unassembled subunits are determinants of ER retention in many cases, although the mechanism of the TMD-mediated sorting of unassembled subunits remains elusive. We studied a yeast iron transporter complex on the cell surface as a new model system for ER quality control. When Fet3p, a transmembrane subunit, is not assembled with the other membrane subunit, Ftr1p, unassembled Fet3p is exclusively localized to the ER at steady state. The TMD of Fet3p contains a determinant for this process. However, pulse-chase analysis and in vitro budding assays indicate that unassembled Fet3p rapidly escapes from the ER. Furthermore, Rer1p, a retrieval receptor for ER-resident membrane proteins in the Golgi, is responsible for the TMD-dependent ER retrieval of unassembled Fet3p. These findings provide clear evidence that the ER quality control of unassembled membrane proteins can be achieved by retrieval from the Golgi and that Rer1p serves as a specific sorting receptor in this process.

Bibliography

Sato, M., Sato, K., & Nakano, A. (2004). Endoplasmic Reticulum Quality Control of Unassembled Iron Transporter Depends on Rer1p-mediated Retrieval from the Golgi. Molecular Biology of the Cell, 15(3), 1417â1424.

Authors 3

Miyuki Sato (first)
Ken Sato (additional)
Akihiko Nakano (additional)

References 49 Referenced 50

Dates

Type	When
Created	21 years, 8 months ago (Dec. 29, 2003, 8:14 p.m.)
Deposited	4 years, 2 months ago (June 13, 2021, 1:50 p.m.)
Indexed	1 month, 4 weeks ago (July 1, 2025, 1:25 p.m.)
Issued	21 years, 5 months ago (March 1, 2004)
Published	21 years, 5 months ago (March 1, 2004)
Published Print	21 years, 5 months ago (March 1, 2004)

Funders 0

None

BibTeX

@article{Sato_2004, title={Endoplasmic Reticulum Quality Control of Unassembled Iron Transporter Depends on Rer1p-mediated Retrieval from the Golgi}, volume={15}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e03-10-0765}, DOI={10.1091/mbc.e03-10-0765}, number={3}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Sato, Miyuki and Sato, Ken and Nakano, Akihiko}, year={2004}, month=mar, pages={1417–1424} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        1
      ]
    ],
    "date-time": "2025-07-01T17:25:20Z",
    "timestamp": 1751390720610
  },
  "reference-count": 49,
  "publisher": "American Society for Cell Biology (ASCB)",
  "issue": "3",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        3
      ]
    ]
  },
  "abstract": "<jats:p>Endoplasmic reticulum (ER) quality control is a conserved process by which misfolded or unassembled proteins are selectively retained in the endoplasmic reticulum (ER). Failure in oligomerization of multisubunit membrane proteins is one of the events that triggers ER quality control. The transmembrane domains (TMDs) of unassembled subunits are determinants of ER retention in many cases, although the mechanism of the TMD-mediated sorting of unassembled subunits remains elusive. We studied a yeast iron transporter complex on the cell surface as a new model system for ER quality control. When Fet3p, a transmembrane subunit, is not assembled with the other membrane subunit, Ftr1p, unassembled Fet3p is exclusively localized to the ER at steady state. The TMD of Fet3p contains a determinant for this process. However, pulse-chase analysis and in vitro budding assays indicate that unassembled Fet3p rapidly escapes from the ER. Furthermore, Rer1p, a retrieval receptor for ER-resident membrane proteins in the Golgi, is responsible for the TMD-dependent ER retrieval of unassembled Fet3p. These findings provide clear evidence that the ER quality control of unassembled membrane proteins can be achieved by retrieval from the Golgi and that Rer1p serves as a specific sorting receptor in this process.</jats:p>",
  "DOI": "10.1091/mbc.e03-10-0765",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        12,
        30
      ]
    ],
    "date-time": "2003-12-30T01:14:01Z",
    "timestamp": 1072746841000
  },
  "page": "1417-1424",
  "source": "Crossref",
  "is-referenced-by-count": 50,
  "title": "Endoplasmic Reticulum Quality Control of Unassembled Iron Transporter Depends on Rer1p-mediated Retrieval from the Golgi",
  "prefix": "10.1091",
  "volume": "15",
  "author": [
    {
      "given": "Miyuki",
      "family": "Sato",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, Saitama 351-0198, Japan"
        }
      ]
    },
    {
      "given": "Ken",
      "family": "Sato",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, Saitama 351-0198, Japan"
        }
      ]
    },
    {
      "given": "Akihiko",
      "family": "Nakano",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Molecular Membrane Biology Laboratory, RIKEN Discovery Research Institute, Saitama 351-0198, Japan"
        },
        {
          "name": "Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan"
        }
      ]
    }
  ],
  "member": "1076",
  "reference": [
    {
      "key": "REF1",
      "doi-asserted-by": "crossref",
      "unstructured": "Askwith, C., Eide, D., Van Ho, A., Bernard, P.S., Li, L., Davis-Kaplan, S., Sipe, D.M., and Kaplan, J. (1994). TheFET3gene ofS. cerevisiaeencodes a multi-copper oxidase required for ferrous iron uptake.Cell76, 403-410.",
      "DOI": "10.1016/0092-8674(94)90346-8"
    },
    {
      "key": "REF2",
      "doi-asserted-by": "crossref",
      "unstructured": "Bednarek, S.Y., Ravazzola, M., Hosobuchi, M., Amherdt, M., Perrelet, A., Schekman, R., and Orci, L. (1995). COPI- and COPII-coated vesicles bud directly from the endoplasmic reticulum in yeast.Cell83, 1183-1196.",
      "DOI": "10.1016/0092-8674(95)90144-2"
    },
    {
      "key": "REF3",
      "doi-asserted-by": "crossref",
      "unstructured": "Boehm, J., Ulrich, H.D., Ossig, R., and Schmitt, H.D. (1994). Kex2-dependent invertase secretion as a tool to study the targeting of transmembrane proteins which are involved in ER-Golgi transport in yeast.EMBO J.13, 3696-3710.",
      "DOI": "10.1002/j.1460-2075.1994.tb06679.x"
    },
    {
      "key": "REF4",
      "doi-asserted-by": "crossref",
      "unstructured": "Bonifacino, J.S., Cosson, P., and Klausner, R.D. (1990). Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains.Cell63, 503-513.",
      "DOI": "10.1016/0092-8674(90)90447-M"
    },
    {
      "key": "REF5",
      "doi-asserted-by": "crossref",
      "unstructured": "Bonifacino, J.S., Cosson, P., Shah, N., and Klausner, R.D. (1991). Role of potentially charged transmembrane residues in targeting proteins for retention and degradation within the endoplasmic reticulum.EMBO J.10, 2783-2793.",
      "DOI": "10.1002/j.1460-2075.1991.tb07827.x"
    },
    {
      "key": "REF6",
      "doi-asserted-by": "crossref",
      "unstructured": "Brodsky, J.L., and McCracken, A.A. (1999). ER protein quality control and proteasome-mediated protein degradation.Semin. Cell Dev. Biol.10, 507-513.",
      "DOI": "10.1006/scdb.1999.0321"
    },
    {
      "key": "REF7",
      "doi-asserted-by": "crossref",
      "unstructured": "Cosson, P., Lankford, S.P., Bonifacino, J.S., and Klausner, R.D. (1991). Membrane protein association by potential intramembrane charge pairs.Nature351, 414-416.",
      "DOI": "10.1038/351414a0"
    },
    {
      "key": "REF8",
      "doi-asserted-by": "crossref",
      "unstructured": "Dancis, A., Yuan, D.S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., and Klausner, R.D. (1994). Molecular characterization of a copper transport protein inS. cerevisiae: an unexpected role for copper in iron transport.Cell76, 393-402.",
      "DOI": "10.1016/0092-8674(94)90345-X"
    },
    {
      "key": "REF9",
      "doi-asserted-by": "crossref",
      "unstructured": "Doms, R.W., Keller, D.S., Helenius, A., and Balch, W.E. (1987). Role for adenosine triphosphate in regulating the assembly and transport of vesicular stomatitis virus G protein trimers.J. Cell Biol.105, 1957-1969.",
      "DOI": "10.1083/jcb.105.5.1957"
    },
    {
      "key": "REF10",
      "doi-asserted-by": "crossref",
      "unstructured": "Ellgaard, L., and Helenius, A. (2003). Quality control in the endoplasmic reticulum.Nat. Rev. Mol. Cell. Biol.4, 181-191.",
      "DOI": "10.1038/nrm1052"
    },
    {
      "key": "REF11",
      "doi-asserted-by": "crossref",
      "unstructured": "Ellgaard, L., Molinari, M., and Helenius, A. (1999). Setting the standards: quality control in the secretory pathway.Science286, 1882-1888.",
      "DOI": "10.1126/science.286.5446.1882"
    },
    {
      "key": "REF12",
      "unstructured": "Fullekrug, J., Boehm, J., Rottger, S., Nilsson, T., Mieskes, G., and Schmitt, H.D. (1997). Human Rer1 is localized to the Golgi apparatus and complements the deletion of the homologous Rer1 protein ofSaccharomyces cerevisiae.Eur. J. Cell Biol.74, 31-40."
    },
    {
      "key": "REF13",
      "unstructured": "Guthrie, C., and Fink., G. (1991). Guide to yeast genetics and molecular biology.Methods Enzymol.194, 182-187."
    },
    {
      "key": "REF14",
      "doi-asserted-by": "crossref",
      "unstructured": "Hammond, C., and Helenius, A. (1994). Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus.J. Cell Biol.126, 41-52.",
      "DOI": "10.1083/jcb.126.1.41"
    },
    {
      "key": "REF15",
      "doi-asserted-by": "crossref",
      "unstructured": "Haynes, C.M., Caldwell, S., and Cooper, A.A. (2002). AnHRD/DER-independent ER quality control mechanism involves Rsp5p-dependent ubiquitination and ER-Golgi transport.J. Cell Biol.158, 91-101.",
      "DOI": "10.1083/jcb.200201053"
    },
    {
      "key": "REF16",
      "doi-asserted-by": "crossref",
      "unstructured": "Hennecke, S., and Cosson, P. (1993). Role of transmembrane domains in assembly and intracellular transport of the CD8 molecule.J. Biol. Chem.268, 26607-26612.",
      "DOI": "10.1016/S0021-9258(19)74355-5"
    },
    {
      "key": "REF17",
      "doi-asserted-by": "crossref",
      "unstructured": "Hong, E., Davidson, A.R., and Kaiser, C.A. (1996). A pathway for targeting soluble misfolded proteins to the yeast vacuole.J. Cell Biol.135, 623-633.",
      "DOI": "10.1083/jcb.135.3.623"
    },
    {
      "key": "REF18",
      "doi-asserted-by": "crossref",
      "unstructured": "Hsu, V.W., Yuan, L.C., Nuchtern, J.G., Lippincott-Schwartz, J., Hammerling, G.J., and Klausner, R.D. (1991). A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules.Nature352, 441-444.",
      "DOI": "10.1038/352441a0"
    },
    {
      "key": "REF19",
      "doi-asserted-by": "crossref",
      "unstructured": "Jackson, M.R., Nillson, T., and Peterson, P.A. (1993). Retrieval of transmembrane proteins to the endoplasmic reticulum.J. Cell Biol.121, 317-333.",
      "DOI": "10.1083/jcb.121.2.317"
    },
    {
      "key": "REF20",
      "unstructured": "Kaiser, C., Michaelis, S., and Mitchell, A. (1994).Methods in Yeast Genetics, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press."
    },
    {
      "key": "REF21",
      "doi-asserted-by": "crossref",
      "unstructured": "Letourneur, F., and Cosson, P. (1998). Targeting to the endoplasmic reticulum in yeast cells by determinants present in transmembrane domains.J. Biol. Chem.273, 33273-33278.",
      "DOI": "10.1074/jbc.273.50.33273"
    },
    {
      "key": "REF22",
      "doi-asserted-by": "crossref",
      "unstructured": "Letourneur, F., Gaynor, E.C., Hennecke, S., Demolliere, C., Duden, R., Emr, S.D., Riezman, H., and Cosson, P. (1994). Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum.Cell79, 1199-1207.",
      "DOI": "10.1016/0092-8674(94)90011-6"
    },
    {
      "key": "REF23",
      "doi-asserted-by": "crossref",
      "unstructured": "Letourneur, F., Hennecke, S., Demolliere, C., and Cosson, P. (1995). Steric masking of a dilysine endoplasmic reticulum retention motif during assembly of the human high affinity receptor for immunoglobulin E.J. Cell Biol.129, 971-978.",
      "DOI": "10.1083/jcb.129.4.971"
    },
    {
      "key": "REF24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.9.10.2767"
    },
    {
      "key": "REF25",
      "doi-asserted-by": "crossref",
      "unstructured": "Massaad, M.J., Franzusoff, A., and Herscovics, A. (1999). The processing alpha1, 2-mannosidase ofSaccharomyces cerevisiaedepends on Rer1p for its localization in the endoplasmic reticulum.Eur. J. Cell Biol.78, 435-440.",
      "DOI": "10.1016/S0171-9335(99)80070-3"
    },
    {
      "key": "REF26",
      "doi-asserted-by": "crossref",
      "unstructured": "Nehls, S., Snapp, E.L., Cole, N.B., Zaal, K.J., Kenworthy, A.K., Roberts, T.H., Ellenberg, J., Presley, J.F., Siggia, E., and Lippincott-Schwartz, J. (2000). Dynamics and retention of misfolded proteins in native ER membranes.Nat. Cell Biol.2, 288-295.",
      "DOI": "10.1038/35010558"
    },
    {
      "key": "REF27",
      "doi-asserted-by": "crossref",
      "unstructured": "Nishikawa, S., and Nakano, A. (1993). Identification of a gene required for membrane protein retention in the early secretory pathway.Proc. Natl. Acad. Sci. USA90, 8179-8183.",
      "DOI": "10.1073/pnas.90.17.8179"
    },
    {
      "key": "REF28",
      "unstructured": "Orlean, P. (1997). Biogenesis of yeast wall and surface components. In: The Molecular and Cellular Biology of the YeastSaccharomyces cerevisiae, vol3, ed. J.R. Pringle, J.R. Broach, and E.W. Jones, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 229-362."
    },
    {
      "key": "REF29",
      "doi-asserted-by": "crossref",
      "unstructured": "Reth, M., Hombach, J., Wienands, J., Campbell, K.S., Chien, N., Justement, L.B., and Cambier, J.C. (1991). The B-cell antigen receptor complex.Immunol. Today12, 196-201.",
      "DOI": "10.1016/0167-5699(91)90053-V"
    },
    {
      "key": "REF30",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.6.11.1459"
    },
    {
      "key": "REF31",
      "doi-asserted-by": "crossref",
      "unstructured": "Sato, M., Sato, K., and Nakano, A. (1996). Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain.J. Cell Biol.134, 279-293.",
      "DOI": "10.1083/jcb.134.2.279"
    },
    {
      "key": "REF32",
      "doi-asserted-by": "crossref",
      "unstructured": "Sato, K., Sato, M., and Nakano, A. (1997). Rer1p as common machinery for the endoplasmic reticulum localization of membrane proteins.Proc. Natl. Acad. Sci. USA94, 9693-9698.",
      "DOI": "10.1073/pnas.94.18.9693"
    },
    {
      "key": "REF33",
      "doi-asserted-by": "crossref",
      "unstructured": "Sato, K., Sato, M., and Nakano, A. (2001). Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is dynamically localized to the Golgi apparatus by coatomer.J. Cell Biol.152, 935-944.",
      "DOI": "10.1083/jcb.152.5.935"
    },
    {
      "key": "REF34",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e02-12-0777"
    },
    {
      "key": "REF35",
      "doi-asserted-by": "crossref",
      "unstructured": "Sato, K., Ueda, T., and Nakano, A. (1999). TheArabidopsis thaliana RER1gene family: its potential role in the endoplasmic reticulum localization of membrane proteins.Plant Mol. Biol.41, 815-824.",
      "DOI": "10.1023/A:1006329828395"
    },
    {
      "key": "REF36",
      "doi-asserted-by": "crossref",
      "unstructured": "Semenza, J.C., Hardwick, K.G., Dean, N., and Pelham, H.R. (1990). ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway.Cell61, 1349-1357.",
      "DOI": "10.1016/0092-8674(90)90698-E"
    },
    {
      "key": "REF37",
      "doi-asserted-by": "crossref",
      "unstructured": "Sikorski, R.S., and Hieter, P. (1989). A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA inSaccharomyces cerevisiae.Genetics122, 19-27.",
      "DOI": "10.1093/genetics/122.1.19"
    },
    {
      "key": "REF38",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.01-07-0322"
    },
    {
      "key": "REF39",
      "doi-asserted-by": "crossref",
      "unstructured": "Stearman, R., Yuan, D.S., Yamaguchi-Iwai, Y., Klausner, R.D., and Dancis, A. (1996). A permease-oxidase complex involved in high-affinity iron uptake in yeast.Science271, 1552-1557.",
      "DOI": "10.1126/science.271.5255.1552"
    },
    {
      "key": "REF40",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.3.2.129"
    },
    {
      "key": "REF41",
      "doi-asserted-by": "crossref",
      "unstructured": "Teckman, J.H., and Perlmutter, D.H. (1996). The endoplasmic reticulum degradation pathway for mutant secretory proteins alpha1-antitrypsin Z and S is distinct from that for an unassembled membrane protein.J. Biol. Chem.271, 13215-13220.",
      "DOI": "10.1074/jbc.271.22.13215"
    },
    {
      "key": "REF42",
      "doi-asserted-by": "crossref",
      "unstructured": "Tsai, B., Ye, Y., and Rapoport, T.A. (2002). Retro-translocation of proteins from the endoplasmic reticulum into the cytosol.Nat. Rev. Mol. Cell. Biol.3, 246-255.",
      "DOI": "10.1038/nrm780"
    },
    {
      "key": "REF43",
      "doi-asserted-by": "crossref",
      "unstructured": "Vashist, S., Kim, W., Belden, W.J., Spear, E.D., Barlowe, C., and Ng, D.T. (2001). Distinct retrieval and retention mechanisms are required for the quality control of endoplasmic reticulum protein folding.J. Cell Biol.155, 355-368.",
      "DOI": "10.1083/jcb.200106123"
    },
    {
      "key": "REF44",
      "doi-asserted-by": "crossref",
      "unstructured": "Ward, C.L., Omura, S., and Kopito, R.R. (1995). Degradation of CFTR by the ubiquitin-proteasome pathway.Cell83, 121-127.",
      "DOI": "10.1016/0092-8674(95)90240-6"
    },
    {
      "key": "REF45",
      "doi-asserted-by": "crossref",
      "unstructured": "Wuestehube, L.J., and Schekman, R.W. (1992). Reconstitution of transport from endoplasmic reticulum to Golgi complex using endoplasmic reticulum-enriched membrane fraction from yeast.Methods Enzymol.219, 124-136.",
      "DOI": "10.1016/0076-6879(92)19015-X"
    },
    {
      "key": "REF46",
      "doi-asserted-by": "crossref",
      "unstructured": "Yuan, D.S., Stearman, R., Dancis, A., Dunn, T., Beeler, T., and Klausner, R.D. (1995). The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake.Proc. Natl. Acad. Sci. USA92, 2632-2636.",
      "DOI": "10.1073/pnas.92.7.2632"
    },
    {
      "key": "REF47",
      "doi-asserted-by": "crossref",
      "unstructured": "Zubenko, G.S., Park, F.J., and Jones, E.W. (1983). Mutations inPEP4locus ofSaccharomyces cerevisiaeblock final step in maturation of two vacuolar hydrolases.Proc. Natl. Acad. Sci. USA80, 510-514.",
      "DOI": "10.1073/pnas.80.2.510"
    },
    {
      "key": "REF48",
      "doi-asserted-by": "crossref",
      "unstructured": "Zuber, C., Fan, J.Y., Guhl, B., Parodi, A., Fessler, J.H., Parker, C., and Roth, J. (2001). Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates involvement of pre-Golgi intermediates in protein quality control.Proc. Natl. Acad. Sci. USA98, 10710-10715.",
      "DOI": "10.1073/pnas.191359198"
    },
    {
      "key": "REF49",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.11.12.4227"
    }
  ],
  "container-title": "Molecular Biology of the Cell",
  "original-title": [],
  "language": "en",
  "deposited": {
    "date-parts": [
      [
        2021,
        6,
        13
      ]
    ],
    "date-time": "2021-06-13T17:50:22Z",
    "timestamp": 1623606622000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.molbiolcell.org/doi/10.1091/mbc.e03-10-0765"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        3
      ]
    ]
  },
  "references-count": 49,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2004,
          3
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1091/mbc.e03-10-0765"
  ],
  "URL": "http://dx.doi.org/10.1091/mbc.E03-10-0765",
  "relation": {},
  "ISSN": [
    "1059-1524",
    "1939-4586"
  ],
  "subject": [],
  "container-title-short": "MBoC",
  "published": {
    "date-parts": [
      [
        2004,
        3
      ]
    ]
  }
}