Pannexin

Pannexins are a family of transmembrane proteins that form large-pore channels in the plasma membrane of cells. They are related to the innexin family found in invertebrates and the connexin family found in vertebrates, all of which form gap junction channels. However, unlike connexins, pannexin channels are generally thought to function as single-membrane channels rather than forming intercellular connections.

Pannexins are characterized by four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. Three mammalian pannexin isoforms have been identified: Pannexin 1 (Panx1), Pannexin 2 (Panx2), and Pannexin 3 (Panx3). These isoforms exhibit different tissue distributions and functional properties, suggesting specialized roles in various physiological processes.

Panx1 is the most widely studied pannexin isoform and is expressed in a variety of tissues, including the brain, spinal cord, heart, and immune system. It has been implicated in diverse cellular functions, including ATP release, cell signaling, inflammation, apoptosis, and taste perception. Activation of Panx1 channels can lead to the release of ATP into the extracellular space, which can then act as a signaling molecule to activate purinergic receptors on neighboring cells. This ATP release can be triggered by various stimuli, such as mechanical stress, changes in membrane potential, or activation of inflammatory pathways.

Panx2 is primarily expressed in the central nervous system, particularly in the brain. Its function is less well understood than that of Panx1, but it is thought to play a role in neuronal development, synaptic plasticity, and potentially in neurological disorders.

Panx3 is expressed in cartilage, bone, skin, and reproductive tissues. It is involved in chondrocyte differentiation, bone formation, and epidermal differentiation. Its role in forming functional channels remains debated, and some studies suggest it may interact with other proteins rather than functioning solely as a channel.

Pannexins are implicated in a variety of physiological and pathological conditions. Dysregulation of pannexin channel activity has been linked to neurological disorders, inflammatory diseases, cardiovascular diseases, and cancer. As such, pannexins are emerging as potential therapeutic targets for these conditions. Further research is needed to fully elucidate the specific roles of each pannexin isoform in different tissues and disease states.