The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Alternative RNA Splicing Generates a Glycosylphosphatidylinositol-anchored Form of Ceruloplasmin in Mammalian Brain
Open accessAbstract
Ceruloplasmin is a copper-containing ferroxidase that is essential for normal iron homeostasis. Whereas ceruloplasmin in plasma is produced and secreted by hepatocytes, in the brain a glycosylphosphatidylinositol (GPI)-anchored form of ceruloplasmin is expressed on the surface of astrocytes. By using a cDNA cloning approach, we have now determined that the GPI-anchored form of ceruloplasmin is generated by alternative RNA splicing. The splicing occurs downstream of exon 18 and replaces the C-terminal 5 amino acids of the secreted form with an alternative 30 amino acids that signal GPI anchor addition. RNase protection analysis demonstrates that the GPI-anchored form is the major form in the brain, whereas the secreted form predominates in the liver. Individuals with aceruloplasminemia, a hereditary deficiency of ceruloplasmin, have severe iron deposition in a number of organs, including the brain where it results in neurodegeneration. Therefore, this novel GPI-anchored form of ceruloplasmin is likely to play an important role in iron metabolism in the central nervous system.
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“in hepatocytes derived from HIF-1α-knockout mice, hepcidin expression in response to iron deficiency was increased (242).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [242]
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“HIF-1α was shown to bind to TfR1 HRE.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [242]
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“hepatocytes and liver samples from mice with deleted von Hip-pel-Lindau (VHL), which is the negative regulator of HIF-1, were iron deficient and showed increased expression of Fpn (Fig. 7) (242).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [242]
In the citing paper
“HIF-1 has been implicated in the transcriptional regulation of hepcidin in response to hypoxia (242).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [242]
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HOW GLYCOSYL-PHOSPHATIDYLINOSITOL-ANCHORED MEMBRANE PROTEINS ARE MADE
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Research works printed but not linked: 3
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- Levin, 1998, Invest. Ophthalmol. & Visual Sci., 39, 157
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Items 201–202 of 202
Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases
Liu, X., Jia, L., Wu, K., Chen, M., Sun, J., Yang, C., Xu, C., Sun, J., Wang, J., & Dai, L. (2026) · MedComm · doi:10.1002/mco2.70766
Metadata
- Authors
- Patel, B. N., Dunn, R. J., & David, S.
- Affiliations
- Montreal General Hospital (CA)
- Corresponding author
- David, Samuel
- ORCID
- David, Samuel
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 275
- Issue
- 6
- Pages
- 4305-4310
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2057172958
- Cited by
- 202
- References
- 37
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 4
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ceruloplasmin, alternative splicing, glycosylphosphatidylinositol anchoring, brain, astrocytes, aceruloplasminemia, iron homeostasis, iron accumulation, neurodegeneration, liver
- MeSH terms
- Amino Acid Sequence, Animals, Brain, Cell Line, Ceruloplasmin, Cloning, Molecular, Humans, Immunohistochemistry, Iron, Liver, Membrane Proteins, Molecular Sequence Data, Type C Phospholipases, Ribonucleases, RNA, Messenger, Transfection, Gene Expression, Sequence Alignment, Glycosylphosphatidylinositols, Alternative Splicing, Phosphatidylinositol Diacylglycerol-Lyase
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