The DOI matches its Crossref record; 43 of the 46 references it cites were found in a registry or an index.
The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing
Open accessAbstract
The low-density lipoprotein receptor-related protein (LRP) has recently been implicated in numerous intracellular signaling functions, as well as in Alzheimer's disease pathogenesis. Studies have shown that the beta-amyloid precursor protein (APP) interacts with LRP and that this association may impact the production of amyloid beta-protein (Abeta). In this report, we provide evidence that LRP regulates trafficking of intracellular proteins independently of its lipoprotein receptor functions. We show that in the absence of LRP, Abeta production, APP secretion, APP internalization, turnover of full-length APP and stability of APP C-terminal fragments are affected. Importantly, these changes are not APP isoform dependent. Using deletion constructs, the critical region in LRP that modulates APP processing was mapped to a seven peptide domain around the second NPXY domain (residues 4504-4510). Therefore, we propose a model by which LRP functionally modulates APP processing, including those steps critical for Abeta production, through interactions of the cytosolic domains.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, unlike LDLR, LRP1 is an APP binding protein that influences APP endocytic trafficking and cellular distribution such that processing to Aβ and its extracellular release is enhanced (Pietrzik et al., 2002; Ulery et al., 2000).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Pietrzik et al., 2002
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, an interaction between the C-terminal domain of APP and LRP, mediated by the cytoplasmic adaptor protein Fe65, impacts APP internalization (18 -23).”
From The Low Density Lipoprotein Receptor-related Protein (LRP) Is a Novel β-Secretase (BACE1) Substrate (2005) · cites this paper as [20]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Since LRP1 is known to increase the production of Aβ peptide (Ulery et al., 2000; Pietrzik et al., 2002), LRP1-deficient cell lines were chosen to eliminate any possible contribution of LRP1 to this process.”
From LRAD3, A Novel Low-Density Lipoprotein Receptor Family Member That Modulates Amyloid Precursor Protein Trafficking (2011) · cites this paper as Pietrzik et al., 2002
The cited source says what the claim attributes to it.
In the citing paper
“Co-transfection with LC did not enhance BACE internalization from the cell surface in LRP-null CHO cells (13-5-1) in contrast to known enhancement of APP endocytosis with LC (20).”
From The Low Density Lipoprotein Receptor-related Protein (LRP) Is a Novel β-Secretase (BACE1) Substrate (2005) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Likely, the multiple alternative functions assigned to this receptor in AD, including intracellular APP transport (Ulery et al., 2000; Pietrzik et al., 2002), blockade of APP signaling (Kinoshita et al., 2003), or Aβ shunt across the blood-brain-barrier (Deane et al., 2004) complicate interpretation of the available experimental data.”
From The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain (2013) · cites this paper as Pietrzik et al., 2002
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
Morgenstern, J. P., & Land, H. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.12.3587 · Cited by 2,099
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413
A Transcriptively Active Complex of APP with Fe65 and Histone Acetyltransferase Tip60
Cao, X., & Südhof, T. C. (2001) · Science · doi:10.1126/science.1058783 · Cited by 1,202
Identification of a Novel Aspartic Protease (Asp 2) as β-Secretase
Hussain, I., Powell, D., Howlett, D. R., Tew, D. G., Meek, T. D., Chapman, C., Gloger, I. S., Murphy, K. E., Southan, C. D., Ryan, D. M., et al. (1999) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1999.0811 · Cited by 1,080
Hiesberger, T., Trommsdorff, M., Howell, B. W., Goffinet, A., Mumby, M. C., Cooper, J. A., & Herz, J. (1999) · Neuron · doi:10.1016/s0896-6273(00)80861-2 · Cited by 916
Evidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 829
Self-citationDistinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides
Hartmann, T., Bieger, S. C., Brühl, B., Tienari, P. J., Ida, N., Allsop, D., Roberts, G. W., Masters, C. L., Dotti, C. G., Unsicker, K., et al. (1997) · Nature Medicine · doi:10.1038/nm0997-1016 · Cited by 719
Proteolytic processing and cell biological functions of the amyloid precursor protein
Strooper, B. D., & Annaert, W. G. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.11.1857 · Cited by 643
Trommsdorff, M., Borg, J.-P., Margolis, B., & Herz, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.50.33556 · Cited by 453
Cited by
Sorted by citations
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075
LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.017 · Cited by 828
Lillis, A. P., Van Duyn, L. B., Murphy-Ullrich, J. E., & Strickland, D. K. (2008) · Physiological Reviews · doi:10.1152/physrev.00033.2007 · Cited by 669
Andersen, O. M., Reiche, J., Schmidt, V., Gotthardt, M., Spoelgen, R., Behlke, J., von Arnim, C. A. F., Breiderhoff, T., Jansen, P., Wu, X., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503689102 · Cited by 655
The Neurobiology of Dopamine Signaling
Girault, J., & Greengard, P. (2004) · Archives of Neurology · doi:10.1001/archneur.61.5.641 · Cited by 454
Metadata
- Authors
- Pietrzik, C. U., Busse, T., Merriam, D. E., Weggen, S., & Koo, E. H.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Koo, Edward H.
- Venue
- The EMBO Journal
- Published
- 2002-11-01
- Volume
- 21
- Issue
- 21
- Pages
- 5691-5700
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC131065
- OpenAlex
- W2069323313
- Cited by
- 198
- References
- 46
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 9 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 14
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Health Assistance Foundation
- National Institutes of Health
- National Institute on Aging (AG 12376, R01AG012376)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- low density lipoprotein receptor-related protein, APP processing, amyloid precursor protein, amyloid-beta production, APP secretion, APP C-terminal fragments, NPXY motif, cytoplasmic domain, Alzheimer's disease, protein trafficking
- MeSH terms
- Animals, Cell Line, Cytoplasm, Enzyme-Linked Immunosorbent Assay, Fibroblasts, Precipitin Tests, Protein Processing, Post-Translational, Blotting, Western, Amyloid beta-Protein Precursor, DNA, Complementary, Low Density Lipoprotein Receptor-Related Protein-1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
