CoChat
Sign Up
Cited by 655Alzheimer's disease research and treatmentsCellular transport and secretionNeuroinflammation and Neurodegeneration Mechanisms

Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein

Open access
Andersen, Olav M., Reiche, Juliane, Schmidt, Vanessa, Gotthardt, Michael, Spoelgen, Robert, Behlke, Joachim, von Arnim, Christine A. F., Breiderhoff, Tilman +11 more·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0503689102PMC PMC1224625
Open this paper in CoChat — free account

Abstract

sorLA (sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduced in the brain of patients with Alzheimer's disease (AD), we tested involvement of this receptor in intracellular transport and processing of the amyloid precursor protein (APP) to the amyloid β-peptide (Aβ), the principal component of senile plaques. We demonstrate that sorLA interacts with APP in vitro and in living cells and that both proteins colocalize in endosomal and Golgi compartments. Overexpression of sorLA in neurons causes redistribution of APP to the Golgi and decreased processing to Aβ, whereas ablation of sorLA expression in knockout mice results in increased levels of Aβ in the brain similar to the situation in AD patients. Thus, sorLA acts as a sorting receptor that protects APP from processing into Aβ and thereby reduces the burden of amyloidogenic peptide formation. Consequently, reduced receptor expression in the human brain may increase Aβ production and plaque formation and promote spontaneous AD.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0503689102

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • LR11/SorLA sequesters APP in the trans-Golgi network, decreasing the amount of APP in post-Golgi compartments and the plasma membrane.

    “LR11/SorLA sequesters APP in the trans-Golgi network, decreasing the amount of APP in post-Golgi compartments and the plasma membrane (Andersen et al., 2005; Schmidt et al., 2007).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Andersen et al., 2005

    The Results show that sorLA confines APP to Golgi-associated compartments and significantly reduces APP at the cell surface; the Discussion likewise says it impairs APP transport to the surface. The paper does not specifically establish sequestration in the trans-Golgi network or measure a decrease in APP across post-Golgi compartments. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • SORL1 shuttles APP from early endosomes back to the Golgi apparatus and subsequently impairs its trafficking to the cell surface.

    “Interestingly, SORL1 has also been described to shuttle APP from early endosomes back to the Golgi apparatus and to subsequently impair its trafficking to the cell surface [1, 114].”

    From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [1]

    The Results show that sorLA overexpression reduces APP at the cell surface, and the Discussion says sorLA confines APP to Golgi compartments. But the Discussion presents rerouting APP from early endosomes to the Golgi as one possible mechanism, not an established trafficking route; it also offers impaired transport of newly made APP as an alternative. Page numbers were not supplied. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Overexpression of SORLA in neuronal cells blocks amyloidogenic processing and reduces Aβ production, whereas loss of SORLA increases extracellular Aβ levels and plaque deposition in several AD mouse models.

    “Overexpression of SORLA in neuronal cells can block amyloidogenic processing and reduce Aβ production [485], whereas loss of SORLA increased extracellular Aβ levels and plaque deposition in several AD mouse models [486, 487].”

    From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [486]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 25

  1. [1]Hermans-Borgmeyer, I., Hampe, W., Schinke, B., Methner, A., Nykjaer, A., Susens, U., Fenger, U., Herbarth, B. & Schaller, H. C. (1998) Mech. Dev. 70, 65-76. [DOI] [PubMed] [Google Scholar]
  2. [2]Motoi, Y., Aizawa, T., Haga, S., Nakamura, S., Namba, Y. & Ikeda, K. (1999) Brain Res. 833, 209-215. [DOI] [PubMed] [Google Scholar]
  3. [3]Jacobsen, L., Madsen, P., Moestrup, S. K., Lund, A. H., Tommerup, N., Nykjaer, A., Sottrup-Jensen, L., Gliemann, J. & Petersen, C. M. (1996) J. Biol. Chem. 271, 31379-31383. [DOI] [PubMed] [Google Scholar]
  4. [4]Yamazaki, H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W. J. & Saito, Y. (1996) J. Biol. Chem. 271, 24761-24768. [DOI] [PubMed] [Google Scholar]
  5. [5]Marcusson, E. G., Horazdovsky, B. F., Cereghino, J. L., Gharakhanian, E. & Emr, S. D. (1994) Cell 77, 579-586. [DOI] [PubMed] [Google Scholar]
  6. [6]Nykjaer, A., Lee, R., Teng, K. K., Jansen, P., Madsen, P., Nielsen, M. S., Jacobsen, C., Kliemannel, M., Schwarz, E., Willnow, T. E., et al. (2004) Nature 427, 843-848. [DOI] [PubMed] [Google Scholar]
  7. [7]Hampe, W., Urny, J., Franke, I., Hoffmeister-Ullerich, S. A., Herrmann, D., Petersen, C. M., Lohmann, J. & Schaller, H. C. (1999) Development (Cambridge, U.K.) 126, 4077-4086. [DOI] [PubMed] [Google Scholar]
  8. [8]Jacobsen, L., Madsen, P., Nielsen, M. S., Geraerts, W. P., Gliemann, J., Smit, A. B. & Petersen, C. M. (2002) FEBS Lett. 511, 155-158. [DOI] [PubMed] [Google Scholar]
  9. [9]Scherzer, C. R., Offe, K., Gearing, M., Rees, H. D., Fang, G., Heilman, C. J., Schaller, C., Bujo, H., Levey, A. I. & Lah, J. J. (2004) Arch. Neurol. 61, 1200-1205. [DOI] [PubMed] [Google Scholar]
  10. [10]De Strooper, B. & Annaert, W. (2000) J. Cell Sci. 113, Part 11, 1857-1870. [DOI] [PubMed] [Google Scholar]
  11. [11]Andersen, O. M., Christensen, L. L., Christensen, P. A., Sørensen, E. S., Jacobsen, C., Moestrup, S. K., Etzerodt, M. & Thøgersen, H. C. (2000) J. Biol. Chem. 275, 21017-21024. [DOI] [PubMed] [Google Scholar]
  12. [12]Behlke, J., Ristau, O. & Schonfeld, H. J. (1997) Biochemistry 36, 5149-5156. [DOI] [PubMed] [Google Scholar]
  13. [13]Chang, Y., Tesco, G., Jeong, W. J., Lindsley, L., Eckman, E. A., Eckman, C. B., Tanzi, R. E. & Guenette, S. Y. (2003) J. Biol. Chem. 278, 51100-51107. [DOI] [PubMed] [Google Scholar]
  14. [14]von Arnim, C. A., Tangredi, M. M., Peltan, I. D., Lee, B. M., Irizarry, M. C., Kinoshita, A. & Hyman, B. T. (2004) J. Cell Sci. 117, 5437-5445. [DOI] [PubMed] [Google Scholar]
  15. [15]Johnson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 1550-1555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. [16]Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N. P., Gerard, C., Hama, E., Lee, H. J. & Saido, T. C. (2001) Science 292, 1550-1552. [DOI] [PubMed] [Google Scholar]
  17. [17]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 286, 735-741. [DOI] [PubMed] [Google Scholar]
  18. [18]Caporaso, G. L., Takei, K., Gandy, S. E., Matteoli, M., Mundigl, O., Greengard, P. & De Camilli, P. (1994) J. Neurosci. 14, 3122-3138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. [19]Haass, C., Hung, A. Y., Schlossmacher, M. G., Teplow, D. B. & Selkoe, D. J. (1993) J. Biol. Chem. 268, 3021-3024. [PubMed] [Google Scholar]
  20. [20]Yamazaki, T., Selkoe, D. J. & Koo, E. H. (1995) J. Cell Biol. 129, 431-442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [21]Peraus, G. C., Masters, C. L. & Beyreuther, K. (1997) J. Neurosci. 17, 7714-7724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [22]Khvotchev, M. & Sudhof, T. C. (2004) J. Biol. Chem. 279, 47101-47108. [DOI] [PubMed] [Google Scholar]
  23. [23]Xu, H., Greengard, P. & Gandy, S. (1995) J. Biol. Chem. 270, 23243-23245. [DOI] [PubMed] [Google Scholar]
  24. [24]Pietrzik, C. U., Busse, T., Merriam, D. E., Weggen, S. & Koo, E. H. (2002) EMBO J. 21, 5691-5700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. [25]Ho, A. & Sudhof, T. C. (2004) Proc. Natl. Acad. Sci. USA 101, 2548-2553. [DOI] [PMC free article] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Andersen, O. M., Reiche, J., Schmidt, V., Gotthardt, M., Spoelgen, R., Behlke, J., von Arnim, C. A. F., Breiderhoff, T., Jansen, P., Wu, X., Bales, K. R., Cappai, R., Masters, C. L., Gliemann, J., Mufson, E. J., Hyman, B. T., Paul, S. M., Nykjær, A., & Willnow, T. E.
Affiliations
  • Rush University Medical Center (US)
  • Max Delbrueck Center for Molecular Medicine, D-13125 Berlin, Germany; Massachusetts General Hospital, Charlestown, MA 02129; Lilly Research Laboratories, Indianapolis, IN 46285; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612; Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus, Denmark; and Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-09-07
Volume
102
Issue
38
Pages
13461-13466
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0503689102
PMC
PMC1224625
OpenAlex
W2119487442
Cited by
655
References
25
Citations by year
2026: 23 · 2025: 24 · 2024: 26 · 2023: 26 · 2022: 28 · 2021: 35 · 2020: 38 · 2019: 28 · 2018: 20 · 2017: 25 · 2016: 40 · 2015: 27 · 2014: 35 · 2013: 35 · 2012: 41
FWCI
19.18
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › 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
SorLA, LR11, amyloid precursor protein, amyloid-beta, Alzheimer's disease, sorting receptor, neuronal trafficking, Golgi apparatus, endosomes, APP processing, amyloid plaques, protein-protein interaction, knockout mice
MeSH terms
Alzheimer Disease, Animals, Brain, Cricetulus, Golgi Apparatus, Cricetinae, Humans, Protein Processing, Post-Translational, Receptors, LDL, Endosomes, CHO Cells, Amyloid beta-Protein Precursor, Mice, Knockout, Protein Transport, LDL-Receptor Related Proteins, Membrane Transport Proteins, Mice, Plaque, Amyloid

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