title: The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum.
abstract: The sorting of proteins to the appropriate compartment is one of the most fundamental cellular processes. We found that in the model organism Caenorhabditis elegans, correct cotranslational endoplasmic reticulum (ER) transport required the suppressor activity of the nascent polypeptide-associated complex (NAC). NAC did not affect the accurate targeting of ribosomes to ER translocons mediated by the signal recognition particle (SRP) pathway but inhibited additional unspecific contacts between ribosomes and translocons by blocking their autonomous binding affinity. NAC depletion shortened the life span of Caenorhabditis elegans, caused global mistargeting of translating ribosomes to the ER, and provoked incorrect import of mitochondrial proteins into the ER lumen, resulting in a strong impairment of protein homeostasis in both compartments. Thus, the antagonistic targeting activity of NAC is important in vivo to preserve the robustness and specificity of cellular protein-sorting routes.
authors: Department of Biology, Institute of Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.
authors: Martin
authors: M
authors: Gamerdinger
authors: Department of Biology, Institute of Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.
authors: Marie Anne
authors: MA
authors: Hanebuth
authors: Department of Biology, Applied Bioinformatics Laboratory, University of Konstanz, 78457 Konstanz, Germany.
authors: Tancred
authors: T
authors: Frickey
authors: Department of Biology, Institute of Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany. elke.deuerling@uni-konstanz.de.
authors: Elke
authors: E
authors: Deuerling
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D060746:Endoplasmic Reticulum-Associated Degradation; D006706:Homeostasis; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D014176:Protein Biosynthesis; D021381:Protein Transport; D012270:Ribosomes / Q000378:metabolism; D018271:Signal Recognition Particle / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D018271:Signal Recognition Particle; C096099:nascent-polypeptide-associated complex