Evidence map›Paper›PMID 8895567›Full record

ArticleThe EMBO journal1996

The beta-amyloid domain is essential for axonal sorting of amyloid precursor protein.

P J Tienari, B De Strooper, E Ikonen, M Simons, A Weidemann, C Czech, T Hartmann, N Ida, G Multhaup, C L Masters and 3 more

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 130 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. UV irradiation accelerates amyloid precursor protein (APP) processing and disrupts APP axonal transport.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Trafficking and proteolytic processing of APP.Cold Spring Harbor perspectives in medicine · 2012
    Review
  17. Review
  18. Article
  19. Physiological functions of APP family proteins.Cold Spring Harbor perspectives in medicine · 2012
    Review
  20. Roles of Brain Angiotensin II in Cognitive Function and Dementia.International journal of hypertension · 2012
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

P J TienariCell Biology Programme, European Molecular Biology Laboratories (EMBL), Heidelberg, Germany.
B De Strooper
E Ikonen
M Simons
A Weidemann
C Czech
T Hartmann
N Ida
G Multhaup
C L Masters
F Van Leuven
K Beyreuther
C G Dotti
European Molecular Biology Laboratory · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have analysed the axonal sorting signals of amyloid precursor protein (APP). Wild-type and mutant versions of human APP were expressed in hippocampal neurons using the Semliki forest virus system. We show that wild-type APP and mutations implicated in Alzheimer's disease and another brain beta-amyloidosis are sorted to the axon. By analysis of deletion mutants we found that the membrane-inserted APP ectodomain but not the cytoplasmic tail is required for axonal sorting. Systematic deletions of the APP ectodomain identified two regions required for axonal delivery: one encoded by exons 11-15 in the carbohydrate domain, the other encoded by exons 16-17 in the juxtamembraneous beta-amyloid domain. Treatment of the cells with the N-glycosylation inhibitor tunicamycin induced missorting of wild-type APP, supporting the importance of glycosylation in axonal sorting of APP. The data revealed a hierarchy of sorting signals on APP: the beta-amyloid-dependent membrane proximal signal was the major contributor to axonal sorting, while N-glycosylation had a weaker effect. Furthermore, recessive somatodendritic signals, most likely in the cytoplasmic tail, directed the protein to the dendrites when the ectodomain was deleted. Analysis of detergent solubility of APP and another axonally delivered protein, hemagglutinin, demonstrated that only hemagglutinin formed CHAPS-insoluble complexes, suggesting distinct mechanisms of axonal sorting for these two proteins. This study is the first delineation of sorting requirements of an axonally targeted protein in polarized neurons and indicates that the beta-amyloid domain plays a major role in axonal delivery of APP.

Indexed as

Alzheimer DiseaseAmino Acid SequenceAmyloid beta-Protein PrecursorAmyloidosisAnimalsAxonal TransportAxonsCell MembraneCell PolarityCells, CulturedCholic AcidsDetergentsEpitopesGlycosylationHemagglutinins, ViralHippocampus3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonateAmyloid beta-Protein PrecursorCholic AcidsDetergentsEpitopesHemagglutinins, ViralProto-Oncogene Proteins c-mycRecombinant Fusion ProteinsTunicamycin

Identifiers

PMID8895567
PMCPMC452266
OpenAlexW1869777169

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.