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PTEN suppresses axon outgrowth by down-regulating the level of detyrosinated microtubules

Christina Kath1,2, Paloma Goni-Oliver1, Rainer Müller3

  • 1Charité -Universtiätsmedizin, Virchowweg 6, Berlin, Germany.

Plos One
|April 5, 2018
PubMed

Insights

Phosphatase and tensin homolog (PTEN) regulates cell growth by stabilizing microtubules. PTEN depletion enhances axon outgrowth by increasing detyrosinated microtubules, revealing a novel role in neuronal development.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • The tumor suppressor PTEN regulates cell growth and migration by modulating the actin cytoskeleton.
  • The role of PTEN in microtubule dynamics and its impact on cell migration and neuronal development remain largely unknown.

Purpose of the Study:

  • To investigate the role of PTEN in regulating microtubule dynamics.
  • To determine the effect of PTEN on neurite and axon outgrowth.
  • To elucidate the function of detyrosinated microtubules in PTEN-mediated cellular processes.

Main Methods:

  • PTEN depletion in fibroblasts and neurons using genetic methods.
  • Analysis of microtubule stability and post-translational modifications (detyrosination).
  • Assessment of cell migration and axon outgrowth.
  • Rescue experiments by reducing detyrosinated microtubule levels.

Main Results:

  • PTEN depletion led to increased levels of stable and detyrosinated microtubules.
  • PTEN-deficient cells exhibited enhanced axon outgrowth.
  • Reducing detyrosinated microtubules rescued the enhanced axon outgrowth phenotype.
  • PTEN suppresses axon outgrowth by down-regulating detyrosinated microtubules.

Conclusions:

  • PTEN plays a novel role in regulating microtubule cytoskeleton stability and detyrosination.
  • Detyrosinated microtubules are critical for axon outgrowth.
  • PTEN's tumor suppressor function may involve microtubule stabilization, impacting cell growth and neurodevelopmental phenotypes.

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