TMEM163 Regulates ATP-Gated P2X Receptor and Behavior.
Elizabeth J Salm1, Patrick J Dunn2, Lili Shan2
1Department of Cellular and Molecular Physiology, Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration and Repair, The Yale Kavli Institute, Yale University School of Medicine, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell Reports
|June 4, 2020
Summary
Researchers identified TMEM163 as a key regulator of ATP-gated ionotropic P2X receptors (P2XRs) in vivo. This discovery highlights TMEM163 as a potential therapeutic target for pain management.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Fast purinergic signaling, mediated by ATP and P2X receptors (P2XRs), plays a role in pain behaviors.
- Observed differences in P2XR properties between cell cultures and in vivo suggest the existence of functional modulators.
Purpose of the Study:
- To identify novel modulators of P2X receptor activity in vivo.
- To investigate the role of identified modulators in neuronal function and pain-related behaviors.
Main Methods:
- Genome-wide open reading frame (ORF) collection and functional screening were employed to identify P2XR modulators.
- Specific assays were used to characterize the modulatory effects of TMEM163 on P2XRs.
Main Results:
- TMEM163 was identified as a specific modulator of P2X receptor channel properties and pharmacology.
- TMEM163 is essential for the full function of neuronal P2XRs and ATP-evoked pain behaviors in vivo.
Conclusions:
- TMEM163 is a critical in vivo modulator of P2X receptors.
- TMEM163 represents a potential therapeutic target for developing novel pain relief medications.
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