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The Dual Roles of Clusterin in Extracellular and Intracellular Proteostasis

Journal Article


Abstract


  • Clusterin (CLU) was the first reported secreted mammalian chaperone and impacts on serious diseases associated with inappropriate extracellular protein aggregation. Many studies have described intracellular CLU in locations outside the secretory system and recent work has shown that CLU can be released into the cytosol during cell stress. In this article, we critically evaluate evidence relevant to the proposed origins of cellular CLU found outside the secretory system, and advance the hypothesis that the cytosolic release of CLU induced by stress serves to facilitate the trafficking of misfolded proteins to the proteasome and autophagy for degradation. We also propose future research directions that could help establish CLU as a unique chaperone performing critical and synergic roles in both intracellular and extracellular proteostasis.

UOW Authors


Publication Date


  • 2021

Citation


  • Satapathy, S., & Wilson, M. R. (2021). The Dual Roles of Clusterin in Extracellular and Intracellular Proteostasis. Trends in Biochemical Sciences, 46(8), 652-660. doi:10.1016/j.tibs.2021.01.005

Scopus Eid


  • 2-s2.0-85100615267

Start Page


  • 652

End Page


  • 660

Volume


  • 46

Issue


  • 8

Abstract


  • Clusterin (CLU) was the first reported secreted mammalian chaperone and impacts on serious diseases associated with inappropriate extracellular protein aggregation. Many studies have described intracellular CLU in locations outside the secretory system and recent work has shown that CLU can be released into the cytosol during cell stress. In this article, we critically evaluate evidence relevant to the proposed origins of cellular CLU found outside the secretory system, and advance the hypothesis that the cytosolic release of CLU induced by stress serves to facilitate the trafficking of misfolded proteins to the proteasome and autophagy for degradation. We also propose future research directions that could help establish CLU as a unique chaperone performing critical and synergic roles in both intracellular and extracellular proteostasis.

UOW Authors


Publication Date


  • 2021

Citation


  • Satapathy, S., & Wilson, M. R. (2021). The Dual Roles of Clusterin in Extracellular and Intracellular Proteostasis. Trends in Biochemical Sciences, 46(8), 652-660. doi:10.1016/j.tibs.2021.01.005

Scopus Eid


  • 2-s2.0-85100615267

Start Page


  • 652

End Page


  • 660

Volume


  • 46

Issue


  • 8