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Adapting Secretory Proteostasis and Function Through the Unfolded Protein Response

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Coordinating Organismal Physiology Through the Unfolded Protein Response

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 414))

Abstract

Cells address challenges to protein folding in the secretory pathway by engaging endoplasmic reticulum (ER)-localized protective mechanisms that are collectively termed the unfolded protein response (UPR). By the action of the transmembrane signal transducers IRE1, PERK, and ATF6, the UPR induces networks of genes whose products alleviate the burden of protein misfolding. The UPR also plays instructive roles in cell differentiation and development, aids in the response to pathogens, and coordinates the output of professional secretory cells. These functions add to and move beyond the UPR’s classical role in addressing proteotoxic stress. Thus, the UPR is not just a reaction to protein misfolding, but also a fundamental driving force in physiology and pathology. Recent efforts have yielded a suite of chemical genetic methods and small molecule modulators that now provide researchers with both stress-dependent and -independent control of UPR activity. Such tools provide new opportunities to perturb the UPR and thereby study mechanisms for maintaining proteostasis in the secretory pathway. Numerous observations now hint at the therapeutic potential of UPR modulation for diseases related to the misfolding and aggregation of ER client proteins. Growing evidence also indicates the promise of targeting ER proteostasis nodes downstream of the UPR. Here, we review selected advances in these areas, providing a resource to inform ongoing studies of secretory proteostasis and function as they relate to the UPR.

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Authors and Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139-4307, USA

    Madeline Y. Wong, Andrew S. DiChiara, Patreece H. Suen, Kenny Chen, Ngoc-Duc Doan & Matthew D. Shoulders

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  1. Madeline Y. Wong
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  2. Andrew S. DiChiara
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  3. Patreece H. Suen
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  4. Kenny Chen
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  5. Ngoc-Duc Doan
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  6. Matthew D. Shoulders
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Corresponding author

Correspondence to Matthew D. Shoulders .

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Editors and Affiliations

  1. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA

    R. Luke Wiseman

  2. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Cole M. Haynes

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Wong, M.Y., DiChiara, A.S., Suen, P.H., Chen, K., Doan, ND., Shoulders, M.D. (2017). Adapting Secretory Proteostasis and Function Through the Unfolded Protein Response. In: Wiseman, R., Haynes, C. (eds) Coordinating Organismal Physiology Through the Unfolded Protein Response. Current Topics in Microbiology and Immunology, vol 414. Springer, Cham. https://doi.org/10.1007/82_2017_56

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