Evidence map›Paper›PMID 20463227›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010

Alterations of EHD1/EHD4 protein levels interfere with L1/NgCAM endocytosis in neurons and disrupt axonal targeting.

Chan Choo C Yap, Zofia M Lasiecka, Steven Caplan, Bettina Winckler

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Significance of transcytosis in Alzheimer's disease: BACE1 takes the scenic route to axons.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015
    Article
  12. Review
  13. Article
  14. Maturational conversion of dendritic early endosomes and their roles in L1-mediated axon growth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014
    Article
  15. Article
  16. X11/Mint genes control polarized localization of axonal membrane proteins in vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013
    Article
  17. Doublecortin (DCX) mediates endocytosis of neurofascin independently of microtubule binding.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012
    Article
  18. Review
  19. Article
  20. 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

4 authors at 2 institutions in 1 country.

Chan Choo C YapDepartment of Neuroscience, University of Virginia Medical School, Charlottesville, Virginia 22936, USA.
Zofia M Lasiecka
Steven Caplan
Bettina Winckler
University of Virginia · USUniversity of Nebraska Medical Center · US

Funding

SUPPRESSIVE ROLE OF TGFBETA IN METASTASIS OF COLON CANCERP20RR018759 · NCRR · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SIMPSON, MELANIE A. · 2003 to 2011
$17.9M
Molecular Mechanisms Controlling Endocytic RecyclingR01GM074876 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI CAPLAN, STEVEN H · 2006 to 2015
$2.6M
Targeting Pathways of Axonal Cell Adhesion MoleculesR01GM086913 · NIGMS · UNIVERSITY OF VIRGINIA · PI WINCKLER, BETTINA R · 2009 to 2012
$1.4M
NCRR NIH HHS P20 RR018759NIGMS NIH HHS GM074876NIGMS NIH HHS GM086913NIGMS NIH HHS R01 GM074876NIGMS NIH HHS R01 GM086913
6 · The paper itself

Abstract

Axon growth is regulated by many proteins, including adhesion molecules, which need to be trafficked correctly to axons. The adhesion molecule L1/neuron-glia cell adhesion molecule (NgCAM) travels to axons via an endocytosis-dependent pathway (transcytosis), traversing somatodendritic endosomes. The Eps15 homology domain (EHD) family proteins (EHD1-EHD4) play important roles in endosomal recycling and possibly in endocytosis. We investigated whether EHD1 regulates L1/NgCAM trafficking in neurons. Both short hairpin-mediated downregulation and overexpression of EHD1 led to dendritic mistargeting of NgCAM. Downregulation of EHD1 showed increased endosomal accumulation of NgCAM, whereas, surprisingly, overexpression of EHD1 led to impairment of L1/NgCAM internalization in neurons but not in fibroblasts. Transferrin internalization, however, was unaffected. At longer overexpression times of EHD1, NgCAM endocytosis returned to normal, suggesting rapid upregulation of compensatory endocytic pathways. EHD1 is capable of hetero-oligomerization, and an endogenous complex of EHD1 and EHD4 was identified previously. We therefore tested whether short-term overexpression of other EHD family members showed a similar endocytosis defect. Expression of EHD4, but not of EHD3, also caused a defect in L1/NgCAM endocytosis. Oligomerization of EHD1 was required to cause NgCAM endocytosis defects, and simultaneous expression of EHD1 and EHD4 rescued NgCAM endocytosis. Therefore, balanced levels of EHD1-EHD4 are important for NgCAM endocytosis in neurons. Our data suggest that EHD1 plays roles in both endosomal recycling and a specialized endocytosis pathway in neurons used by NgCAM. We propose that EHD1 and EHD4 act as hetero-oligomeric complexes in this pathway.

Indexed as

AnimalsAxonsCell EnlargementCells, CulturedChlorocebus aethiopsCOS CellsEndocytosisEndosomesFibroblastsHippocampusNerve Tissue ProteinsNeural Cell Adhesion Molecule L1NeuronsPC12 CellsRatsSignal TransductionEHD1 protein, ratEhd4 protein, ratNerve Tissue ProteinsNeural Cell Adhesion Molecule L1TransferrinVesicular Transport Proteins

Identifiers

PMID20463227
PMCPMC2905050
OpenAlexW1978427724

What OpenQuestion holds

Textmetadata
LicenceTDM
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.