Evidence map›Paper›PMID 25886013›Full record

ArticleNeural development2015

Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones.

Michael Piper, Aih Cheun Lee, Francisca P G van Horck, Heather McNeilly, Trina Bo Lu, William A Harris, Christine E Holt

Erratum issuedOpen access · goldAbstract readComparative Study
In one paragraph

Article in Neural development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Mutation of the ALS-/FTD-Associated RNA-Binding Protein FUS Affects Axonal Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Regulation and outcomes of localized RNA translation.Wiley interdisciplinary reviews. RNA · 2022
    Review
  9. Review
  10. Article
  11. Review
  12. Axonal mRNA localization and translation: local events with broad roles.Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Striking a balance: PIPExploration of neuroprotective therapy · 2021
    Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Michael PiperDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. m.piper@uq.edu.au.
Aih Cheun LeeDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. orcalee@gmail.com.
Francisca P G van HorckDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. francisca.wollerton@f-star.com.
Heather McNeillyDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. heather.mcneilly@cantab.net.
Trina Bo LuDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. doggieadastra@gmail.com.
William A HarrisDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. wah20@cam.ac.uk.
Christine E HoltDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing street, Cambridge, CB2 3DY, UK. ceh33@cam.ac.uk.
University of Cambridge · GBUniversity of Queensland · AU

Funding

Wellcome Trust 085314/Z/08/ZWellcome Trust 100329
6 · The paper itself

Abstract

backgroundLocal protein synthesis (LPS) via receptor-mediated signaling plays a role in the directional responses of axons to extrinsic cues. An intact cytoskeleton is critical to enact these responses, but it is not known whether the two major cytoskeletal elements, F-actin and microtubules, have any roles in regulating axonal protein synthesis.

resultsHere, we show that pharmacological disruption of either microtubules or actin filaments in growth cones blocks netrin-1-induced de novo synthesis of proteins, as measured by metabolic incorporation of labeled amino acids, implicating both elements in axonal synthesis. However, comparative analysis of the activated translation initiation regulator, eIF4E-BP1, revealed a striking difference in the point of action of the two elements: actin disruption completely inhibited netrin-1-induced eIF4E-BP1 phosphorylation while microtubule disruption had no effect. An intact F-actin, but not microtubule, cytoskeleton was also required for netrin-1-induced activation of the PI3K/Akt/mTOR pathway, upstream of translation initiation. Downstream of translation initiation, microtubules were required for netrin-1-induced activation of eukaryotic elongation factor 2 kinase (eEF2K) and eEF2.

conclusionsTaken together, our results show that while actin and microtubules are both crucial for cue-induced axonal protein synthesis, they serve distinct roles with F-actin being required for the initiation of translation and microtubules acting later at the elongation step.

Indexed as

ActinsAnimalsBridged Bicyclo Compounds, HeterocyclicCarrier ProteinsColchicineCytochalasin DCytoskeletonElongation Factor 2 KinaseGene Expression RegulationGrowth ConesMicrotubulesNerve Growth FactorsNerve Tissue ProteinsNetrin-1NocodazoleOocytesActinsBridged Bicyclo Compounds, HeterocyclicCarrier ProteinsColchicineCytochalasin DeIF4E-BP1 protein, XenopusElongation Factor 2 Kinaselatrunculin BNerve Growth FactorsNerve Tissue ProteinsNetrin-1NocodazolePeptide Elongation Factor 2Phosphatidylinositol 3-KinasesThiazolidinesTubulin ModulatorsTumor Suppressor ProteinsXenopus Proteins

Identifiers

PMID25886013
PMCPMC4350973
OpenAlexW2123006264

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.