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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
Pannexin 1 phosphorylation sites differentially modulate channel activity and physiological outcomes
Brooke L O'Donnell1, Luke S Dunaway1,2, Xuexin Zhang3
1Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
Distinct pannexin 1 (PANX1) phosphorylation sites regulate blood pressure and vascular function by altering channel activity and ATP release. These findings reveal how PANX1 modifications impact hemodynamics and smooth muscle cell responses.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Cell Signaling
Background:
- Pannexin 1 (PANX1) channels in vascular smooth muscle cells (SMCs) are crucial for regulating blood pressure and α-adrenergic constriction.
- PANX1 channel activity is modulated by phosphorylation at specific residues (Y198, S205, Y308), but the physiological relevance of these modifications remains unclear.
Purpose of the Study:
- To investigate the physiological significance of PANX1 phosphorylation at Y198, S205, and Y308 residues in regulating vascular function and hemodynamics.
- To elucidate the distinct roles of PANX1 phosphorylation in channel activity, metabolite release, and blood pressure control.
Main Methods:
- Development and utilization of novel PANX1 phospho-dead mutant mice (Y198F, S205A, Y308F) for physiological assessments.
- Radiotelemetry for blood pressure monitoring, pressure myography for mesenteric artery contractility, and HEK293T cell-based assays for channel activity and ATP release.
- Bulk RNA sequencing and co-immunoprecipitation-mass spectrometry were employed to explore underlying signaling mechanisms.
Main Results:
- PANX1 Y198F mutant mice exhibited decreased blood pressure and impaired α-adrenergic responses, mimicking PANX1 inhibitor effects.
- PANX1 Y308F mutant mice showed increased baseline blood pressure and enhanced α-adrenergic contractility.
- Phosphorylation at Y198 specifically affects phenylephrine-induced ATP release, while S205 and Y308 phosphorylation impact channel current, demonstrating distinct functional roles.
Conclusions:
- Distinct PANX1 phosphorylation sites differentially regulate channel-conducted currents and ATP release, impacting vascular physiology.
- PANX1 phosphorylation at Y198, S205, and Y308 plays critical roles in modulating vascular smooth muscle cell function and overall blood pressure regulation.
- These findings highlight the complex interplay between PANX1 post-translational modifications and cardiovascular homeostasis.
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