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Growth Cone Tctp Is Dynamically Regulated by Guidance Cues

Cláudio Gouveia Roque1,2, Christine E Holt1

  • 1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.

Frontiers in Molecular Neuroscience
|November 22, 2018
PubMed

Insights

Translationally controlled tumor protein (Tctp) is regulated by guidance cues in retinal ganglion cell growth cones. However, local Tctp synthesis in axons is not essential for retinal axon development in vivo.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Translationally controlled tumor protein (Tctp) is implicated in retinal circuitry formation and axon development.
  • Tctp transcripts are highly enriched in the axonal compartment of retinal ganglion cells (RGCs), suggesting local regulation is important.
  • The specific role of axonal Tctp in axon development programs remains unclear.

Purpose of the Study:

  • To investigate the regulation of Tctp levels in RGC growth cones by guidance cues.
  • To determine the necessity of locally synthesized Tctp for retinal axon growth and guidance in vivo.

Main Methods:

  • Utilized live imaging and translation reporters to monitor Tctp synthesis in growth cones.
  • Examined Tctp level changes in response to Netrin-1 and Ephrin-A1.
  • Assessed the impact of inhibiting de novo Tctp synthesis on retinal projections in vivo.

Main Results:

  • Growth cone Tctp levels dynamically changed in response to Netrin-1 (increasing, dependent on protein synthesis and mTORC1) and Ephrin-A1 (decreasing, an mTORC1 inhibitor).
  • Netrin-1-induced Tctp synthesis in growth cones is mediated by a specific 3'UTR mRNA isoform.
  • Acute inhibition of de novo Tctp synthesis in axons did not affect retinal projection advancement in vivo.

Conclusions:

  • Tctp levels in RGC growth cones are rapidly and oppositely regulated by guidance cues Netrin-1 and Ephrin-A1.
  • Local Tctp synthesis in axons is not required for normal retinal axon growth and guidance during development.
Keywords:
Ephrin-A1Netrin-1Tctpaxon guidancegrowth conemTORCprotein translationretinal ganglion cell

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