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Journal article

Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates

  • Bernasconi, Riccardo Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Galli, Carmela Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Calanca, Verena Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Nakajima, Toshihiro St. Marianna University School of Medicine, Kanagawa 216-8512, Japan
  • Molinari, Maurizio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, 1015 Lausanne, Switzerland
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    2010
Published in:
  • The journal of cell biology. - 2010, vol. 188, no. 2, p. 223–235
English Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD). The presence of structural lesions in the luminal, transmembrane, or cytosolic domains determines the classification of misfolded polypeptides as ERAD-L, -M, or -C substrates and results in selection of distinct degradation pathways. In this study, we show that disposal of soluble (nontransmembrane) polypeptides with luminal lesions (ERAD-LS substrates) is strictly dependent on the E3 ubiquitin ligase HRD1, the associated cargo receptor SEL1L, and two interchangeable ERAD lectins, OS-9 and XTP3-B. These ERAD factors become dispensable for degradation of the same polypeptides when membrane tethered (ERAD-LM substrates). Our data reveal that, in contrast to budding yeast, tethering of mammalian ERAD-L substrates to the membrane changes selection of the degradation pathway.
Language
  • English
Classification
Medicine
License
CC BY-NC-SA
Open access status
hybrid
Identifiers
  • RERO DOC 324213
  • ARK ark:/12658/srd1318922
Persistent URL
https://n2t.net/ark:/12658/srd1318922
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