Pannexin: from discovery to bedside in 11±4 years?

Area of Science:

• Molecular biology
• Cell biology
• Neuroscience

Background:

• Pannexin1 (Panx1) was initially identified as a gap junction protein.
• Panx1 functions as a mechanosensitive, ATP-permeable channel in the cell membrane.
• It facilitates molecular exchange between the cytoplasm and extracellular space.

Purpose of the Study:

• To present evidence supporting Panx1's role as a major ATP release channel.
• To highlight Panx1's involvement in innate immunity and inflammatory processes.
• To propose Panx1 as a therapeutic target for CNS trauma and stroke.

Main Methods:

• Review of existing literature and experimental evidence.
• Analysis of Panx1 expression patterns in ATP-releasing cells.
• Examination of Panx1 channel pharmacology and genetic modification effects.

Main Results:

• Panx1 is expressed in various ATP-releasing cells, including erythrocytes and airway epithelial cells.
• Panx1 channel pharmacology aligns with observed ATP release characteristics.
• Panx1's role in inflammasome-mediated cell death and inflammatory amplification is established.

Conclusions:

• Panx1 is a key mediator of non-vesicular ATP release.
• Panx1, in conjunction with P2X7 receptors, influences innate immunity and cell death pathways.
• Panx1 inhibitors, like probenecid, warrant consideration for therapeutic use in stroke and CNS trauma.