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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

A novel function for p53: regulation of growth cone motility through interaction with Rho kinase

Qingyu Qin1, Michel Baudry, Guanghong Liao

  • 1Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766-1854, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 24, 2009
PubMed

Insights

The tumor suppressor p53 regulates neuronal growth cone motility. Inhibiting p53 function collapses axonal growth cones, while overexpression enlarges them, revealing a new role in neuronal development.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • The transcription factor p53 is a known tumor suppressor involved in regulating cell proliferation and migration.
  • Its role in the behavior of postmitotic neurons, particularly axonal growth, remains largely unexplored.

Purpose of the Study:

  • To investigate the function of p53 in controlling cell motility within postmitotic neurons.
  • To determine if p53 influences axonal growth cone behavior and its underlying molecular mechanisms.

Main Methods:

  • Utilized primary hippocampal neurons to study p53 expression and function.
  • Employed inhibitors, small interfering RNAs, and dominant-negative forms to modulate p53 activity.
  • Assessed axonal growth cone morphology and distribution using specific antibodies and microscopy.
  • Investigated the involvement of Rho kinase (ROCK) signaling pathway.

Main Results:

  • p53 isoforms were highly and specifically expressed in axons and axonal growth cones.
  • Inhibition of p53 function led to axonal growth cone collapse, whereas p53 overexpression resulted in larger growth cones.
  • Deletion of the p53 nuclear export signal impaired axonal distribution and induced growth cone collapse.
  • p53 inhibition-induced growth cone collapse was mitigated by the Rho kinase (ROCK) inhibitor Y27632.

Conclusions:

  • p53 plays a critical role in regulating axonal growth cone behavior in postmitotic neurons.
  • p53 functions by suppressing Rho kinase (ROCK) activity, thereby controlling axonal motility.
  • These findings uncover a novel function for p53 beyond its established role in tumor suppression.

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