Pannexin

Pannexins (from Latin 'pan' — all, throughout, and 'nexus' — bond, connection) are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments (such as ATP and sulforhodamine B).

Function
Pannexins are involved in early stages of innate immunity through their interaction with the P2X7 purinergic receptor. Activation of the pannexin channel through binding of ATP to P2X7 receptor leads to the release of IL-1β.

Hypothetical roles of pannexins in the nervous system include participating in sensory processing, synchronization between hippocampus and cortex, hippocampal plasticity, and propagation of the calcium waves. Calcium waves are supported by glial cells, which help maintain and modulate neuronal metabolism. According to one of the hypothesis, Pannexins also may participate in pathological reactions, including the neural damage after ischemia and subsequent cell death.

Pannexin channels are involved in the release of ATP from cells.

Relationship to connexins
Intercellular gap junctions in vertebrates are formed by the connexin family of proteins. Structurally, pannexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 intracellular loop, along with intracellular N- and C-terminal tails. Despite this shared topology, the protein families do not share enough sequence similarity to confidently infer common ancestry.

Clinical significance
Pannexins may be involved in the process of tumorigenesis. Particularly, PANX2 expression levels predict post diagnosis survival for patients with glial tumors.

Probenecid, a well-established drug for the treatment of gout, allows for discrimination between channels formed by connexins and pannexins. Probenecid did not affect channels formed by connexins.

Subtypes
Three pannexins have been described in Chordates: Panx1, Panx2 and Panx3.