Evidence map›Paper›PMID 24373286›Full record

ArticleCell reports2013

A function for EHD family proteins in unidirectional retrograde dendritic transport of BACE1 and Alzheimer's disease Aβ production.

Virginie Buggia-Prévot, Celia G Fernandez, Vinod Udayar, Kulandaivelu S Vetrivel, Aureliane Elie, Jelita Roseman, Verena A Sasse, Margaret Lefkow, Xavier Meckler, Sohinee Bhattacharyya and 8 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
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  10. Induction ofFrontiers in aging neuroscience · 2022
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  13. Science translational medicine · 2020
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  14. Article
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  17. Article
  18. Complex formation of APP with GABANature communications · 2019
    Article
  19. Article
  20. The Endolysosomal System and Proteostasis: From Development to Degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Review
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

18 authors at 5 institutions in 3 countries.

Virginie Buggia-PrévotDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Celia G FernandezCommittee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA.
Vinod UdayarSystems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
Kulandaivelu S VetrivelDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Aureliane ElieDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Jelita RosemanDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Verena A SasseCentre for Prions and Protein Folding Diseases, Departments of Medicine and Psychiatry, University of Alberta, Edmonton, AB T6G 2M8, Canada.
Margaret LefkowCommittee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA.
Xavier MecklerDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Sohinee BhattacharyyaEppley Institute for Research in Cancer and Allied Diseases and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Manju GeorgeEppley Institute for Research in Cancer and Allied Diseases and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Satyabrata KarCentre for Prions and Protein Folding Diseases, Departments of Medicine and Psychiatry, University of Alberta, Edmonton, AB T6G 2M8, Canada.
Vytautas P BindokasDepartment of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, IL 60637, USA.
Angèle T ParentDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.
Lawrence RajendranSystems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
Hamid BandEppley Institute for Research in Cancer and Allied Diseases and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Robert VassarDepartment of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Gopal ThinakaranDepartments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: gopal@uchicago.edu.
University of Chicago · USUniversity of Nebraska Medical Center · USUniversity of Alberta · CAUniversity of Zurich · CHNorthwestern University · US

Funding

STRUCTURAL AND FUNCTIONAL ANALYSIS OF PRESENILINSR01AG019070 · NIA · UNIVERSITY OF CHICAGO · PI THINAKARAN, GOPAL · 2001 to 2015
$4.9M
BACE1 as a Therapeutic Target for Alzheimer's DiseaseR01AG022560 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2003 to 2017
$4.6M
TYROSINE KINASE REGULATION VIA PROTEIN DEGRADATIONR01CA087986 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2000 to 2015
$4.2M
TRAINING IN NEURAL SYSTEMST32GM007839 · NIGMS · UNIVERSITY OF CHICAGO · PI MASON, PEGGY · 1985 to 2012
$4.2M
MOLECULAR CONTROL OF EGF RECEPTOR DOWN-REGULATIONR01CA099163 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2003 to 2012
$3.7M
Cell Biology of Presenilin 1 and Associated ProteinsR01AG021495 · NIA · UNIVERSITY OF CHICAGO · PI THINAKARAN, GOPAL · 2002 to 2012
$3.4M
Molecular Neuropathology and Mechanisms of BACE1 Elevation in Alzheimer's DiseaseR01AG030142 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2007 to 2019
$3.1M
Targeting Endocytic Recycling of EGF Receptor in Cancer R01CA105489 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2004 to 2014
$3.0M
BACE1 as a Therapeutic Target for Alzheimer's DiseaseRF1AG022560 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 2019 to 2019
$2.0M
Presenilins and Cell Adhesion MoleculesR01NS055223 · NINDS · UNIVERSITY OF CHICAGO · PI PARENT, ANGELE · 2008 to 2012
$1.7M
ErbB2 Downregulation Through HSP90 InhibitionR01CA116552 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2007 to 2011
$1.4M
Multi-purpose Superresolution Microscope for Core FacilityS10OD010649 · OD · UNIVERSITY OF CHICAGO · PI THINAKARAN, GOPAL · 2012 to 2012
$511k
NCI NIH HHS CA105489NCI NIH HHS CA116552NCI NIH HHS CA87986NCI NIH HHS CA99163NCI NIH HHS R01 CA087986NCI NIH HHS R01 CA099163NCI NIH HHS R01 CA105489NCI NIH HHS R01 CA116552NIA NIH HHS AG019070NIA NIH HHS AG021495NIA NIH HHS AG022560NIA NIH HHS AG030142NIA NIH HHS R01 AG019070NIA NIH HHS R01 AG021495NIA NIH HHS R01 AG022560NIA NIH HHS R01 AG030142NIA NIH HHS RF1 AG022560NIGMS NIH HHS GM07839-30NIGMS NIH HHS T32 GM007839NIH HHS S10 OD010649NINDS NIH HHS NS055223NINDS NIH HHS R01 NS055223
6 · The paper itself

Abstract

Abnormal accumulation of β-secretase (BACE1) in dystrophic neurites and presynaptic β-amyloid (Aβ) production contribute to Alzheimer's disease pathogenesis. Little, however, is known about BACE1 sorting and dynamic transport in neurons. We investigated BACE1 trafficking in hippocampal neurons using live-cell imaging and selective labeling. We report that transport vesicles containing internalized BACE1 in dendrites undergo exclusive retrograde transport toward the soma, whereas they undergo bidirectional transport in axons. Unidirectional dendritic transport requires Eps15-homology-domain-containing (EHD) 1 and 3 protein function. Furthermore, loss of EHD function compromises dynamic axonal transport and overall BACE1 levels in axons. EHD1/3 colocalize with BACE1 and APP β-C-terminal fragments in hippocampal mossy fiber terminals, and their depletion in neurons significantly attenuates Aβ levels. These results demonstrate unidirectional endocytic transport of a dendritic cargo and reveal a role for EHD proteins in neuronal BACE1 transcytosis and Aβ production, processes that are highly relevant for Alzheimer's disease.

Indexed as

Axonal TransportAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCarrier ProteinsCells, CulturedDendritesHEK293 CellsHeLa CellsHippocampusHumansMiceProtein TransportVesicular Transport ProteinsAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, mouseCarrier ProteinsEhd1 protein, mouseEhd3 protein, mouseVesicular Transport Proteins

Identifiers

PMID24373286
PMCPMC3932704
OpenAlexW1974507908

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Registered trials

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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.