Cited by 145Clusterin in disease pathologyHeat shock proteins researchBiomarkers in Disease Mechanisms

Clusterin facilitates in vivo clearance of extracellular misfolded proteins

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Wyatt, Amy R., Yerbury, Justin J., Berghofer, Paula, Greguric, Ivan, Katsifis, Andrew, Dobson, Christopher M., Wilson, Mark R.·2011·Cellular and Molecular Life Sciences

Abstract

The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localization to the liver and that this clearance is delayed by pre-injection with the scavenger receptor inhibitor fucoidan. The CLU-client complexes were found to bind preferentially, in a fucoidan-inhibitable manner, to human peripheral blood monocytes and isolated rat hepatocytes and in the latter cell type were internalized and targeted to lysosomes for degradation. The data suggest, therefore, that CLU plays a key role in an extracellular proteostasis system that recognizes, keeps soluble, and then rapidly mediates the disposal of misfolded proteins.

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Crossref · 10.1007/s00018-011-0684-8

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  • Clusterin is involved in apoptosis, cell proliferation, and clearance of misfolded proteins.

    “Clusterin (CLU), a multifunctional glycoprotein also known as apolipoprotein J, plays a role in several cellular processes including apoptosis, proliferation, and clearance of misfolded proteins (Kim and Choi, 2011,Wang, et al., 2014,Wyatt, et al., 2011)”

    From A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin (2016) · cites this paper as Wyatt, et al., 2011

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Authors
Wyatt, A. R., Yerbury, J. J., Berghofer, P., Greguric, I., Katsifis, A., Dobson, C. M., & Wilson, M. R.
Affiliations
  • University of Wollongong (AU)
  • Australian Nuclear Science and Technology Organisation (AU)
  • University of Cambridge (GB)
Corresponding author
Wilson, Mark R.
Venue
Cellular and Molecular Life Sciences
Published
2011-04-20
Volume
68
Issue
23
Pages
3919-3931
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
OpenAlex
W2077960804
Cited by
145
References
48
Citations by year
2026: 9 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 15 · 2021: 7 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 9 · 2012: 10
FWCI
4.88
Type
journal article
Language
en
Open access
Locations
  • Cellular and Molecular Life Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Online (University of Wollongong) (submittedVersion)
  • The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
  • Figshare (submittedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Oncology › Clusterin in disease pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
clusterin, misfolded proteins, extracellular chaperones, fucoidan, scavenger receptors, hepatocytes, monocytes, lysosomal degradation
MeSH terms
Animals, Citrate (si)-Synthase, Endocytosis, Extracellular Space, Fibrinogen, Glutathione Transferase, Humans, Leukocytes, Mononuclear, Lysosomes, Molecular Weight, Polysaccharides, Reference Values, Structure-Activity Relationship, Tissue Distribution, Rats, Sprague-Dawley, Protein Folding, Molecular Chaperones, Hepatocytes, Clusterin, Rats

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