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Protein Quality Control in the Endoplasmic Reticulum

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Abstract

The site of protein folding and maturation for the majority of proteins that are secreted, localized to the plasma membrane or targeted to endomembrane compartments is the endoplasmic reticulum (ER). It is essential that proteins targeted to the ER are properly folded in order to carry out their function, as well as maintain protein homeostasis, as accumulation of misfolded proteins could lead to the formation of cytotoxic aggregates. Because protein folding is an error-prone process, the ER contains protein quality control networks that act to optimize proper folding and trafficking of client proteins. If a protein is unable to reach its native state, it is targeted for ER retention and subsequent degradation. The protein quality control networks of the ER that oversee this evaluation or interrogation process that decides the fate of maturing nascent chains is comprised of three general types of families: the classical chaperones, the carbohydrate-dependent system, and the thiol-dependent system. The cooperative action of these families promotes protein quality control and protein homeostasis in the ER. This review will describe the families of the ER protein quality control network and discuss the functions of individual members.

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Acknowledgements

This work was supported by the National Institutes of Health under Award No. GM086874 (to D.N.H.); and a Chemistry-Biology Interface Predoctoral training grant (T32 GM008515 to B. M. A.). We would also like to thank Jill Graham for thoughtful comments.

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  1. Department of Biochemistry and Molecular Biology, University of Massachusetts, 240 Thatcher Road, Amherst, MA, 01003, USA

    Benjamin M. Adams, Michela E. Oster & Daniel N. Hebert

  2. Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, 01003, USA

    Benjamin M. Adams & Daniel N. Hebert

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Correspondence to Daniel N. Hebert.

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Adams, B.M., Oster, M.E. & Hebert, D.N. Protein Quality Control in the Endoplasmic Reticulum. Protein J 38, 317–329 (2019). https://doi.org/10.1007/s10930-019-09831-w

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