Clusterin facilitates in vivo clearance of extracellular misfolded proteins
Open accessAbstract
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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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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A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin
Deming, Y., Xia, J., Cai, Y., Lord, J., Holmans, P., Bertelsen, S., Holtzman, D., Morris, J. C., Bales, K., Pickering, E. H., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.009 · Cited by 66 · see citing works
“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).”
BackgroundAsuni, A. A., Gray, B., Bailey, J., Skipp, P., Perry, V. H., & O'Connor, V. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.502690 · Cited by 31 · see citing works
- 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.
- ORCID
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2011-04-20
- Volume
- 68
- Issue
- 23
- Pages
- 3919-3931
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11115182
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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