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Updated: Jan 13, 2026

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PP2Acα regulates cerebellar development via phosphorylation-dependent neuronal programs.

Yifan Li1, Jing Ding1, Simeng Liu1

  • 1Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.

Iscience
|January 9, 2026
PubMed
Summary
This summary is machine-generated.

Protein phosphatase 2A catalytic subunit alpha (PP2Acα) is crucial for cerebellar development. Its absence impairs motor coordination and cognitive function by disrupting neuron growth and organization.

Keywords:
BiochemistryDevelopmental biologyNeuroscience

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Precise control of phosphorylation is essential for cerebellar development.
  • The specific roles of protein phosphatases, like PP2Acα, are not well understood.

Purpose of the Study:

  • To investigate the function of PP2Acα in cerebellar granule neurons.
  • To elucidate the mechanisms by which PP2Acα regulates cerebellar development.

Main Methods:

  • Conditional deletion of the PP2Acα gene (Ppp2ca) in mice using Atoh1-Cre.
  • Histological analysis of cerebellar development.
  • Phosphoproteomic and proteomic profiling of neurons and whole cerebellum.

Main Results:

  • Deletion of PP2Acα led to impaired motor coordination and cognitive deficits.
  • Abnormalities in granule neuron proliferation, migration, and Purkinje cell organization were observed.
  • PP2Acα regulates cell cycle, cytoskeleton, RNA splicing, metabolism, and translation.

Conclusions:

  • PP2Acα is a critical regulator of cerebellar development.
  • It controls phosphorylation and protein homeostasis at cellular and system levels.
  • Provides insights into phosphatase-related neurodevelopmental disorders.