Caenorhabditis Elegans Degenerins and Vertebrate Enac Ion Channels Contain an Extracellular Domain Related to Venom Neurotoxins

Abstract

The DEG/ENaC (DEGenerin/Epithelial Na⁺ Channel) superfamily includes closely related ion channel subunits from divergent species ranging from the simple nematode Caenorhabditis elegans to humans. Members of this protein group play roles in several important processes including transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Structure/function relationships in members of this superfamily are just beginning to be elaborated. Using a bioinformatics approach, we identified a novel structural element in the extracellular region of DEG/ENaC proteins that exhibits significant similarity to venom neurotoxins. Since venom neurotoxins bind to sodium channels at high affinity, we suggest that the related domain embedded in DEG/ENaC channels may interact with other regions of the channel or channel complex to modulate channel function.

Key Words:

• Mechanotransduction
• neurodegeneration
• Kunitz-type protease inhibitors
• anti-epilepsy peptide