A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.
Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress. This process requires recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex ... in the mammalian ER that links these two events. The central component of the complex, Derlin-1, is a homologue of Der1, a yeast protein whose inactivation prevents the elimination of misfolded luminal ER proteins. Derlin-1 associates with different substrates as they move through the membrane, and inactivation of Derlin-1 in C. elegans causes ER stress. Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Animals, Cytosol, Dogs, Endoplasmic Reticulum, Histocompatibility Antigens Class I, Humans, Macromolecular Substances, Membrane Proteins, Molecular Sequence Data, Nuclear Proteins, Protein Folding, Protein Processing, Post-Translational, Protein Transport, RNA-Binding Proteins, Selenoproteins, Viral Proteins
Adenosine Triphosphatases, Amino Acid Sequence, Animals, Cytosol, Dogs, Endoplasmic Reticulum, Histocompatibility Antigens Class I, Humans, Macromolecular Substances, Membrane Proteins, Molecular Sequence Data, Nuclear Proteins, Protein Folding, Protein Processing, Post-Translational, Protein Transport, RNA-Binding Proteins, Selenoproteins, Viral Proteins
Nature
Date: Jun. 24, 2004
PubMed ID: 15215856
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