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.

Automated summary

The fidelity of protein targeting is crucial for proper organelle functioning. The mechanisms by which cells achieve high accuracy in protein localization are not fully understood. This chapter reviews recent progress in understanding the molecular mechanisms and substrate selection of the SRP pathway in mammals, with a focus on the role of the cotranslational chaperone NAC in protein localization.