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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 18, 2009

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The prion protein selectively binds to and modulates the content of purinergic receptor P2X4R

Mariana V Carneiro1, Tatiana A Americo1, Marilia Z P Guimarães2

  • 1Instituto de Biofísica, UFRJ, Rio de Janeiro, Brazil.

Biochemical and Biophysical Research Communications
|March 7, 2016
PubMed

Insights

The prion protein (PrP(C)) interacts with the P2X4 receptor, influencing its levels. This suggests PrP(C) may play a role in proteostasis, crucial for neurodegenerative disease pathogenesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Prion Biology

Background:

  • The GPI-anchored prion protein (PrP(C)) is implicated in neurodegenerative diseases like Transmissible Spongiform Encephalopathies (TSE) and Alzheimer's Disease.
  • PrP(C) has diverse functions and interacts with cell surface receptors, including neurotransmitter receptors.

Purpose of the Study:

  • To investigate the interaction between the prion protein (PrP(C)) and the purinergic receptor P2X4R.
  • To explore the functional consequences of this interaction in transfected cells.

Main Methods:

  • HEK293 cells were transfected to express PrP(C) and P2X4R.
  • Interaction was assessed using overlay and co-immunoprecipitation assays.
  • Co-localization was visualized via confocal microscopy; functional interaction was tested by compound uptake and calcium modulation.

Main Results:

  • PrP(C) bound to P2X4R, with co-localization observed both intracellularly and at the cell surface.
  • Functional assays indicated an interaction, but this was unexpectedly linked to PrP(C)'s selective effect on P2X4R expression levels.
  • PrP(C) appears to regulate the cellular content of P2X4R.

Conclusions:

  • PrP(C) interacts with P2X4R, influencing its expression.
  • This interaction suggests a potential role for PrP(C) in cellular proteostasis.
  • Dysregulation of proteostasis by PrP(C) may contribute to the pathology of neurodegenerative diseases like TSE and Alzheimer's.
Keywords:
NeurodegenerationNeurotransmissionPrionProteostasisScaffold proteinSignal transduction

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