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Proline-Rich Transmembrane Protein 2 Is Variably Expressed Across Excitatory and Inhibitory Neurons in Mouse Motor

Daisuke Hatta1,2, Kaori Watanabe1, Akira Kinoshita2,3

  • 1Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

The Journal of Comparative Neurology
|June 4, 2026
PubMed
Summary

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Proline-rich transmembrane protein 2 (PRRT2) is crucial for movement control. This study reveals PRRT2 is expressed in both excitatory and inhibitory neurons within motor circuits, suggesting broader roles in regulating movement.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Proline-rich transmembrane protein 2 (PRRT2) mutations are linked to paroxysmal kinesigenic dyskinesia (PKD).
  • PRRT2's role extends beyond the cerebellum to basal ganglia motor circuits, regulating dopaminergic activity.
  • The specific neuronal cell types expressing PRRT2 and their functional implications in motor control are not fully understood.

Purpose of the Study:

  • To determine the neurochemical types of neurons expressing PRRT2.
  • To investigate the distribution of PRRT2 in different neuronal populations within motor-related brain regions.

Main Methods:

  • Immunofluorescence staining on mouse midbrain primary neurons.
  • Immunofluorescence staining on mouse brain sections.
Keywords:
Prrt2basal gangliadyskinesiaimmunofluorescencemotor circuit

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  • Analysis of PRRT2 expression in relation to specific neuronal markers (glutamatergic, GABAergic, dopaminergic, cholinergic, Vglut1, Vglut2).

    • Main Results:

    • PRRT2 is primarily expressed in glutamatergic and GABAergic neurons, but not in dopaminergic or cholinergic neurons.
    • PRRT2 shows preferential expression in Vglut1-positive cortical projection neurons and cerebellar granule cells.
    • In the basal ganglia, PRRT2 is found in GABAergic medium spiny neurons, localized to axonal tracts and presynaptic terminals.

    Conclusions:

    • PRRT2 exhibits variable expression across both excitatory and inhibitory neurons in motor circuits.
    • These findings suggest PRRT2 plays diverse roles in regulating neuronal excitability and voluntary movement control.