Proteostasis refers to a delicately tuned balance between the processes of protein synthesis, folding, localization, and the degradation of proteins found inside and outside cells. Our understanding of extracellular proteostasis is rather limited and largely restricted to knowledge of 11 currently established extracellular chaperones (ECs). This review will briefly outline what is known of the established ECs, before moving on to discuss experimental strategies used to identify new members of this growing family, and an examination of a group of putative new ECs identified using one of these approaches. An observation that emerges from an analysis of the expanding number of ECs is that all of these proteins are multifunctional. Strikingly, the armory of activities each possess uniquely suit them as a group to act together at sites of tissue damage, infection, and inflammation to restore homeostasis. Lastly, we highlight outstanding questions to guide future research in this field.
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February 2022
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Cover Image
Cover Image
The highly conserved enzyme IMPDH plays an essential role in purine biosynthesis and is tightly regulated by many different mechanisms. Depicted here are cryo-EM structures of the large retinal splice variant of IMPDH1 in different filament assembly conformations overlaid on a cryo-EM micrograph of IMPDH1 filaments. Cover artwork created by Jesse Hansen.
Review Article|
December 23 2021
Identifying new molecular players in extracellular proteostasis
Sandeep Satapathy;
Sandeep Satapathy
1Blavatnik Institute of Cell Biology, Harvard Medical School, Boston, MA 02115, U.S.A.
2The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, U.S.A.
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Mark R. Wilson
3Molecular Horizons and The School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia
4Illawarra Health and Medical Research Institute, Northfields Avenue, Wollongong, NSW 2522, Australia
Correspondence: Mark R. Wilson (mrw@uow.edu.au)
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Publisher: Portland Press Ltd
Received:
October 14 2021
Revision Received:
December 07 2021
Accepted:
December 09 2021
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem Soc Trans (2022) 50 (1): 321–334.
Article history
Received:
October 14 2021
Revision Received:
December 07 2021
Accepted:
December 09 2021
Citation
Sandeep Satapathy, Mark R. Wilson; Identifying new molecular players in extracellular proteostasis. Biochem Soc Trans 28 February 2022; 50 (1): 321–334. doi: https://doi.org/10.1042/BST20210369
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