Research Article

The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum

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Science  10 Apr 2015:
Vol. 348, Issue 6231, pp. 201-207
DOI: 10.1126/science.aaa5335

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Sorting out cell sorting

The sorting of proteins into appropriate compartments is vital for proper cell function. After its discovery 20 years ago, various potential roles for nascent chain-associated complex (NAC) in the specificity of intracellular protein sorting have been proposed. Until now, no clear phenotypes have been discovered. Gamerdinger et al. explored the role of NAC in protein translocation in Caenorhabditis elegans (see the Perspective by Kramer et al.). They found that NAC prevents the importation of incorrect cargo, such as mitochondrial proteins, into the endoplasmic reticulum.

Science, this issue p. 201; see also p. 182


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.

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