PANX1 (Pannexin 1) is a channel-forming protein that releases ATP and other signaling molecules from cells. It plays important roles in neuroinflammation, synaptic transmission, and cell death pathways relevant to neurodegenerative diseases.
| Property | Value |
|----------|-------|
| UniProt ID | Q9Y5X5 |
| Gene | PANX1 |
| Alternative Names | Pannexin 1, UNQ2519 |
| Molecular Weight | ~42 kDa |
| Subcellular Localization | Plasma membrane, endoplasmic reticulum |
| Protein Family | Pannexin family |
| PDB Structures | 6WBG, 7J |
PANX1 forms:
- Heptameric channel: Seven subunits assemble to form the channel
- Four transmembrane domains: Each subunit contains 4 TMDs
- Two extracellular loops: Involved in channel gating and interactions
- Intracellular N- and C-termini: Regulatory regions
The channel has large pore diameter (~10-20 Å) allowing ATP, ions, and small metabolites to pass.
PANX1 is a major pathway for ATP release:
- Activation by P2X7 receptor stimulation
- Voltage-dependent gating
- Caspase-dependent cleavage and activation
- Purinergic signaling via ATP release
- Calcium wave propagation
- Activation of P2X and P2Y receptors
- Inflammasome activation (caspase-1 dependent)
- IL-1β release
- Phagocyte recruitment
- Caspase-3/7 cleavage of PANX1
- ATP release during apoptosis ("find-me" signals for phagocytes)
- Activation of P2X7 on neighboring cells
-
Neuroinflammation: PANX1 activation in microglia releases ATP, amplifying inflammatory responses.
-
Amyloid-beta Effects: Aβ can activate PANX1 channels, causing:
- Dysregulated calcium influx
- ATP release
- Pro-inflammatory signaling
-
Synaptic Dysfunction: PANX1 overactivity may contribute to synaptic loss.
- Dopaminergic Neuron Vulnerability: PANX1 activation contributes to inflammatory damage
- Inflammasome Activation: PANX1-mediated ATP release activates NLRP3 inflammasome
- Potential Therapeutic Target: Blocking PANX1 may protect dopaminergic neurons
- Motor Neuron Death: PANX1 activation in motor neurons
- Neuroinflammation: Microglial PANX1 contributes to neuroinflammation
- Astrocyte Signaling: PANX1 in astrocytes affects neuronal metabolism
¶ Stroke and TBI
- PANX1 contributes to ischemia-induced cell death
- Blood-brain barrier dysfunction
- Inflammatory responses
- Probenecid: PANX1 blocker used in research
- Carbenoxolone: Gap junction and PANX1 blocker
- BBG (Brilliant Blue G): P2X7/PANX1 inhibitor
- Specific peptides: Panx1-blocking peptides
- Achieving brain penetration
- Specificity of inhibitors
- Understanding isoform-specific functions
| Variant |
Effect |
Disease Association |
| V364I |
Altered channel function |
Epilepsy |
| R75H |
Reduced channel activity |
Variable |