Evidence map›Paper›PMID 23926272›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013

Ordered recruitment of dynactin to the microtubule plus-end is required for efficient initiation of retrograde axonal transport.

Armen J Moughamian, Gregory E Osborn, Jacob E Lazarus, Sandra Maday, Erika L F Holzbaur

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
8.8field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 171 citations in OpenAlex.

  1. Article
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  3. Article
  4. Article
  5. Review
  6. CCSer2 gates dynein activity at the cell periphery.The Journal of cell biology · 2025
    Article
  7. Review
  8. Review
  9. Article
  10. CCSer2 gates dynein activity at the cell periphery.bioRxiv : the preprint server for biology · 2024
    Article
  11. Autophagy initiation triggers p150Cellular and molecular life sciences : CMLS · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Nde1 Promotes Lis1-Mediated Activation of Dynein.bioRxiv : the preprint server for biology · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Article

50 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Armen J MoughamianDepartment of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA.
Gregory E Osborn
Jacob E Lazarus
Sandra Maday
Erika L F Holzbaur
University of Pennsylvania · US

Funding

Training in Alzheimer’s and Age-Related Neurodegenerative DiseasesT32AG000255 · NIA · UNIVERSITY OF PENNSYLVANIA · PI ALICE S CHEN-PLOTKIN, VIRGINIA M LEE · 1997 to 2026
$12.5M
The Interaction of Cytoplasmic Dynein and DynactinR01GM048661 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI HOLZBAUR, ERIKA L · 1993 to 2017
$6.0M
Mechanisms of autophagosome biogenesis and maturation in primary neuronsK99NS082619 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MADAY, SANDRA L. · 2013 to 2014
$180k
Microtubule end-binding proteins in insulin secretion: enhanced efficiency of polF30DK089714 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LAZARUS, JACOB ERIC · 2010 to 2011
$65k
Mutations in the CAP-Gly Domain of p150Glued in NeurodegenerationF31NS073196 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MOUGHAMIAN, ARMEN J. · 2012 to 2012
$19k
NIA NIH HHS T32 AG000255NIA NIH HHS T32AG000255NIDDK NIH HHS F30 DK089714NIDDK NIH HHS F30DK089714NIGMS NIH HHS GM48661NIGMS NIH HHS R01 GM048661NINDS NIH HHS 1K99NS082619NINDS NIH HHS F31 NS073196NINDS NIH HHS F31NS073196NINDS NIH HHS K99 NS082619
6 · The paper itself

Abstract

Long-range retrograde axonal transport in neurons is driven exclusively by the microtubule motor cytoplasmic dynein. The efficient initiation of dynein-mediated transport from the distal axon is critical for normal neuronal function, and neurodegenerative disease-associated mutations have been shown to specifically disrupt this process. Here, we examine the role of dynamic microtubules and microtubule plus-end binding proteins (+TIPs) in the initiation of dynein-mediated retrograde axonal transport using live-cell imaging of cargo motility in primary mouse dorsal root ganglion neurons. We show that end-binding (EB)-positive dynamic microtubules are enriched in the distal axon. The +TIPs EB1, EB3, and cytoplasmic linker protein-170 (CLIP-170) interact with these dynamic microtubules, recruiting the dynein activator dynactin in an ordered pathway, leading to the initiation of retrograde transport by the motor dynein. Once transport has initiated, however, neither the EBs nor CLIP-170 are required to maintain transport flux along the mid-axon. In contrast, the +TIP Lis1 activates transport through a distinct mechanism and is required to maintain processive organelle transport along both the distal and mid-axon. Further, we show that the EB/CLIP-170/dynactin-dependent mechanism is required for the efficient initiation of transport from the distal axon for multiple distinct cargos, including mitochondria, Rab5-positive early endosomes, late endosomes/lysosomes, and TrkA-, TrkB-, and APP-positive organelles. Our observations indicate that there is an essential role for +TIPs in the regulation of retrograde transport initiation in the neuron.

Indexed as

1-Alkyl-2-acetylglycerophosphocholine EsteraseAnimalsAxonal TransportCells, CulturedCytoplasmDynactin ComplexDyneinsFemaleGanglia, SpinalLuminescent ProteinsLysosomal-Associated Membrane Protein 1Lysosomal Membrane ProteinsMaleMiceMicrofilament ProteinsMicrotubule-Associated Proteins1-Alkyl-2-acetylglycerophosphocholine EsteraseActr1a protein, mousecytoplasmic linker protein 170Dynactin ComplexDyneinsEB1 microtubule binding proteinsEB3 protein, mouseLamp1 protein, mouseLuminescent ProteinsLysosomal-Associated Membrane Protein 1Lysosomal Membrane ProteinsMicrofilament ProteinsMicrotubule-Associated ProteinsNeoplasm ProteinsPafah1b1 protein, mouserab5 GTP-Binding ProteinsRNA, Small Interfering

Identifiers

PMID23926272
PMCPMC3735891
OpenAlexW2019255889

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.