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Detection of Axonally Localized mRNAs in Brain Sections Using High-Resolution In Situ Hybridization
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A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment.
Andrew P Anderson1, Sanghyun Kim1, Allison J Melton1
1Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Nature Communications
|December 3, 2025
Summary
Researchers identified Ppp2r2c, a protein phosphatase 2A (PP2A) subunit, concentrated at the axon initial segment (AIS). This subunit modulates neuronal activity and targets the Kv1.2 channel, impacting neuronal excitability.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Protein phosphorylation regulates cytoskeletal and membrane proteins at the axon initial segment (AIS).
- Knowledge of AIS-specific kinases and phosphatases remains limited.
Purpose of the Study:
- Identify novel AIS-specific regulatory subunits of protein phosphatase 2A (PP2A).
- Investigate the role of identified subunits in neuronal function and regulation.
Main Methods:
- Subcellular localization studies in mice.
- Microelectrode array (MEA) system for neuronal activity assessment.
- Phosphoproteomics to identify downstream targets.
Main Results:
- Identified Ppp2r2c, a PP2A B55 regulatory subunit, selectively enriched at the AIS.
- Demonstrated that Ppp2r2c modulates neuronal activity during in vitro development.
- Revealed Kv1.2 potassium channel as a downstream target of Ppp2r2c.
Conclusions:
- Ppp2r2c is a key player in local phospho-regulation at the AIS.
- PP2A-B55 subunits show functional heterogeneity in subcellular localization.
- Ppp2r2c links PP2A activity to neuronal excitability via Kv1.2 channel modulation.
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