Degenerin

Degenerin is a term used to describe a family of mechanosensitive cation channel proteins in animals, collectively known as the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The degenerin proteins were first identified in the nematode Caenorhabditis elegans, where mutations in several degenerin genes cause degeneration of touch receptor neurons and defects in mechanosensation, leading to the name degenerin. Members of the DEG/ENaC family form ion channels permeable to Na+ and other cations and are activated by mechanical force.

Structurally, they typically feature two transmembrane segments with a large extracellular loop and can assemble as homomeric or heteromeric trimers. In C. elegans, channel activity is modulated by extracellular tethering proteins such as MEC-2 and MEC-6, and by other DEG/ENaC subunits such as MEC-4 and MEC-10, which together mediate gentle touch sensation in the worm.

Evolutionarily, the DEG/ENaC family is conserved across animals. In vertebrates, related subunits include epithelial ENaCs (alpha, beta, gamma) involved in transepithelial Na+ transport, and acid-sensing ion channels (ASICs) implicated in synaptic transmission, nociception and mechanosensation. Aberrant activity of these channels can contribute disease processes, such as Liddle syndrome due to gain-of-function ENaC mutations, and ASIC-related pain pathways.

Research on degenerin channels has clarified principles of mechanotransduction and ion-channel gating, including the role of extracellular elements in gating and the importance of channel assembly.