Pannexins 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

Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

 connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments (such as ATP

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 and sulforhodamine B

Sulforhodamine b

Sulforhodamine B or kiton red is a fluorescent dye with uses spanning from laser-induced fluorescence to the quantification of cellular proteins of cultured cells. The red, solid, water-soluble dye is primarily used as a polar tracer.The dye has maximal absorbance at 565 nm light and...

).

Function

Pannexins are involved in early stages of innate immunity through their interaction with the P2X7

P2RX7

P2X purinoceptor 7 is a protein that in humans is encoded by the P2RX7 gene.-Recruitment of pannexin:Activation of the P2RX7 receptor by ATP leads to recruitment of pannexin pores which allow small molecules such as ATP to leak out of cells. This allows further activation of purinergic receptors...

 purinergic receptor. Activation of the pannexin channel through binding of ATP to P2X7 receptor leads to the release of IL-1β

IL1B

Interleukin-1 beta also known as catabolin, is a cytokine protein that in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β.- Function :Interleukin 1 was discovered by Gery in 1972...

.

Hypothetical roles of pannexins in the nervous system include participating in sensory processing, synchronization between hippocampus

Hippocampus

The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

 and cortex

Cerebral cortex

The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

, hippocampal plasticity, and propagation of the calcium waves. Calcium waves are supported by glial cells, which help maintain and modulate neuronal metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

. 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 junction

Gap junction

A gap junction or nexus is a specialized intercellular connection between a multitude of animal cell-types. It directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells....

s in vertebrates are formed by the connexin

Connexin

Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions . Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules...

 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

Probenecid

Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...

, a well-established drug for the treatment of gout

Gout

Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

, allows for discrimination between channels formed by connexin

Connexin

Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions . Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules...

s and pannexins. Probenecid

Probenecid

Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...

did not affect channels formed by connexins.