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

Piper, Michael, Lee, Aih Cheun, van Horck, Francisca, McNeilly, Heather, Lu, Trina Bo, Harris, William and Holt, Christine (2015) Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones. Neural Development, 10 3: 1-13. doi:10.1186/s13064-015-0031-0


Author Piper, Michael
Lee, Aih Cheun
van Horck, Francisca
McNeilly, Heather
Lu, Trina Bo
Harris, William
Holt, Christine
Title Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones
Journal name Neural Development   Check publisher's open access policy
ISSN 1749-8104
Publication date 2015-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s13064-015-0031-0
Open Access Status DOI
Volume 10
Issue 3
Start page 1
End page 13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Abstract Local 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.
Formatted abstract
Background

Local 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.

Results

Here, 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.

Conclusions

Taken 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 100329
085314/Z/08/Z
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
School of Biomedical Sciences Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
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Created: Tue, 10 Mar 2015, 22:25:11 EST by Dr Michael Piper on behalf of School of Biomedical Sciences