Clusterin Is a Ligand for Apolipoprotein E Receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR) and Signals via the Reelin-signaling Pathway
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Clusterin, also known as apolipoprotein J, is a multifunctional glycoprotein with the capacity to interact with a wide range of molecules. Although clusterin has been implicated in a broad spectrum of physiological and pathological processes, such as Alzheimer disease or cancer, its precise functions remain elusive. Here we report, that clusterin binds to apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and is internalized by cells expressing either one of these receptors. Binding of clusterin to these receptors triggers a Reelin-like signal in cells expressing disabled-1 (Dab1). It induces phosphorylation of Dab1, which leads to activation of PI3K/Akt and n-cofilin. Cell proliferation and neuroblast chain formation in subventricular zone (SVZ) explants are compromised when clusterin, which is present in the subventricular zone, is blocked in vitro. These data suggest that in the subventricular zone where Reelin is not present but ApoER2, VLDLR, and Dab1, clusterin might be involved in maintaining neurogenesis in vivo.
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ApoE and ApoJ are known ligands for VLDLR.
“Both ApoE and ApoJ (also called Clusterin)–two apolipoproteins found in cerebrospinal fluid–are known ligands for VLDLR26,53,54.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [53]
The Discussion (page unavailable) states that clusterin binds VLDLR, supporting the ApoJ portion of the claim. The passage comparing VLDLR with the LDL receptor names ApoE as a ligand of the LDL receptor, not VLDLR; no retrieved passage establishes ApoE as a VLDLR ligand. The retrieved passages also do not establish that both proteins are found in cerebrospinal fluid. (LLM, conf=0.85)
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- Authors
- Leeb, C., Eresheim, C., & Nimpf, J.
- Affiliations
- Max Perutz Labs (AT)
- Corresponding author
- Nimpf, Johannes
- ORCID
- Nimpf, Johannes
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 289
- Issue
- 7
- Pages
- 4161-4172
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3924281
- OpenAlex
- W1977064948
- Cited by
- 99
- References
- 5
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 10 · 2014: 5
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- clusterin, ApoER2, VLDLR, Reelin signaling, Disabled-1, PI3K/Akt signaling, subventricular zone, neurogenesis, cell proliferation, receptor internalization, Alzheimer's disease
- MeSH terms
- Reelin Protein, Animals, Cells, Cultured, Humans, Nerve Tissue Proteins, Receptors, LDL, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Midline Thalamic Nuclei, LDL-Receptor Related Proteins, NIH 3T3 Cells, Cell Proliferation, Clusterin, Mice, Neurogenesis, HEK293 Cells
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