pannexins

Pannexins are a family of glycoproteins that form large-pore channels in the plasma membrane of vertebrate cells. They are homologous to innexins, the invertebrate gap-junction proteins, but in most vertebrates they do not form intercellular gap junctions. The human pannexins include PANX1, PANX2, and PANX3. PANX1 is broadly expressed, PANX2 is enriched in the central nervous system, and PANX3 is found in skin and connective tissues, with tissue-specific expression patterns varying by species and developmental stage.

Structure and assembly: Each pannexin subunit has four transmembrane domains, with intracellular N- and C-termini and two extracellular loops. N-linked glycosylation in the first extracellular loop limits docking between pannexin molecules, helping explain why vertebrate pannexins typically function as single-membrane channels rather than forming conventional gap junctions. Panx channels assemble as hexamers, creating pannexons that span the membrane.

Function: Panx channels permit the rapid passage of ions and small metabolites, notably ATP, enabling purinergic signaling. They can be activated by membrane depolarization, mechanical stretch, and various receptor-mediated stimuli. In particular, PANX1 can be opened by P2X7 receptor signaling and by caspase-3/7–mediated cleavage during apoptosis, producing a constitutively open channel.

Physiological and clinical relevance: Panx channels participate in inflammation, immune cell communication, nociception, and neural signaling. They are implicated in ischemic injury, neurodegenerative processes, and certain CNS disorders, including epilepsy in animal models. Because they regulate ATP release and inflammatory signaling, pannexins are studied as potential therapeutic targets, though selective pharmacological inhibitors remain an area of ongoing research.

Evolution and nomenclature: Pannexins are conserved across vertebrates and are distinct from connexins in their typical lack of gap-junction formation in mammals, though their roles can vary by tissue context.