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Src-dependent tyrosine phosphorylation at the tips of growth cone filopodia promotes extension

Estuardo Robles1, Stephanie Woo, Timothy M Gomez

  • 1Department of Anatomy, Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 19, 2005
PubMed

Insights

Dynamic phospho-tyrosine signals in neuronal growth cone filopodia guide axon outgrowth. Src kinase activity and local tyrosine phosphorylation control filopodial dynamics and pathfinding decisions.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Extracellular cues guide axon outgrowth via intracellular signaling pathways controlling growth cone cytoskeleton dynamics.
  • The precise spatial and temporal regulation of these signaling intermediates is not well understood.

Purpose of the Study:

  • To investigate the role of tyrosine phosphorylation dynamics in growth cone filopodial behavior and axon pathfinding.
  • To elucidate the involvement of Src family kinases and Cdc42 signaling in growth cone guidance.

Main Methods:

  • Live imaging of tyrosine phosphorylation in growth cone filopodia.
  • Localization studies of active Src family kinases and p21-activated kinase (PAK).
  • Perturbation of Src activity to assess effects on filopodial dynamics and signaling.

Main Results:

  • Dynamic phospho-tyrosine (PY) signals were observed in filopodia, correlating with extension and retraction.
  • Active Src family kinases localized to filopodial tips, regulating PY signaling and filopodial motility.
  • Guidance cues increased local tyrosine phosphorylation in a Cdc42-dependent manner.
  • Asymmetric Src activity led to altered filopodial motility and PY signaling, promoting repulsive turning.

Conclusions:

  • Local changes in filopodial phospho-tyrosine levels, regulated by Src kinase activity, are critical for growth cone pathfinding.
  • Coordinated activation of cytoskeletal effectors by GTPase binding and Src-mediated phosphorylation dictates growth cone responses to guidance cues.

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