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Published January 2022 | Published
Journal Article Open

Fidelity of Cotranslational Protein Targeting to the Endoplasmic Reticulum


Fidelity of protein targeting is essential for the proper biogenesis and functioning of organelles. Unlike replication, transcription and translation processes, in which multiple mechanisms to recognize and reject noncognate substrates are established in energetic and molecular detail, the mechanisms by which cells achieve a high fidelity in protein localization remain incompletely understood. Signal recognition particle (SRP), a conserved pathway to mediate the localization of membrane and secretory proteins to the appropriate cellular membrane, provides a paradigm to understand the molecular basis of protein localization in the cell. In this chapter, we review recent progress in deciphering the molecular mechanisms and substrate selection of the mammalian SRP pathway, with an emphasis on the key role of the cotranslational chaperone NAC in preventing protein mistargeting to the ER and in ensuring the organelle specificity of protein localization.

Additional Information

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Received: 4 December 2021; Revised: 17 December 2021; Accepted: 18 December 2021; Published: 28 December 2021. This work is funded by grants NSF-1929452 from the National Science Foundation and R01 GM078024 and R35 GM136321 from the National Institute of Health to S.S. Author Contributions: Writing—original draft preparation, S.-o.S.; writing—review and editing, H.-H.H.; visualization, H.-H.H. and S.-o.S. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. The authors declare no conflict of interest.

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August 22, 2023
October 23, 2023