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Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1

Kazuhito Toyo-oka1, Daisuke Mori, Yoshihisa Yano

  • 1Department of Genetic Disease Research and 2Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan.

The Journal of Cell Biology
|March 19, 2008
PubMed

Insights

Protein phosphatase 4 catalytic subunit (PP4c) regulates microtubule organization by dephosphorylating NDEL1 and inhibiting Cdk1. Loss of PP4c disrupts microtubule structure via abnormal NDEL1 phosphorylation and katanin p60 recruitment.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphatase 4 catalytic subunit (PP4c) is crucial for cellular processes, including microtubule (MT) organization.
  • PP4c is a PP2A-related serine/threonine phosphatase involved in diverse signaling pathways.

Purpose of the Study:

  • To elucidate the role of PP4c in microtubule organization.
  • To identify substrates and regulatory mechanisms of PP4c in MT dynamics.

Main Methods:

  • Investigated the interaction between PP4c and NDEL1.
  • Assessed the effect of PP4c disruption on Cdk1 activity and NDEL1 phosphorylation.
  • Examined the impact on microtubule organization and katanin p60 recruitment.
  • Utilized inhibition studies for Cdk1, NDEL1, and katanin p60.

Main Results:

  • PP4c selectively dephosphorylates NDEL1 at Cdk1 phosphorylation sites.
  • PP4c negatively regulates Cdk1 activity at the centrosome.
  • Loss of PP4c causes MT disorganization due to unscheduled Cdk1 activation and abnormal NDEL1 phosphorylation.
  • Excessive katanin p60 recruitment to the centrosome was observed in PP4c-deficient cells.
  • Inhibition of Cdk1, NDEL1, or katanin p60 rescued MT defects.

Conclusions:

  • PP4c plays a critical role in maintaining microtubule organization.
  • A novel regulatory pathway involving PP4c, Cdk1, and NDEL1 controls microtubule dynamics via katanin p60.
  • This mechanism highlights PP4c's function in preventing aberrant Cdk1 activation and subsequent microtubule destabilization.

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