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Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones
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  • 作者:Michael Piper (1) (2)
    Aih Cheun Lee (1) (3)
    Francisca PG van Horck (1)
    Heather McNeilly (1)
    Trina Bo Lu (1)
    William A Harris (1)
    Christine E Holt (1)

    1. Department of Physiology
    ; Development and Neuroscience ; University of Cambridge ; Downing street ; Cambridge ; CB2 3DY ; UK
    2. Current address
    ; The School of Biomedical Sciences and the Queensland Brain Institute ; The University of Queensland ; St Lucia ; QLD ; 4072 ; Australia
    3. Current address
    ; Institute of Neuroscience ; Chinese Academy of Sciences ; Shanghai ; 200031 ; China
  • 刊名:Neural Development
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:10
  • 期:1
  • 全文大小:2,963 KB
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  • 刊物主题:Neurosciences; Developmental Biology;
  • 出版者:BioMed Central
  • ISSN:1749-8104
文摘
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.

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