Functional co-assembly among subunits of cyclic-nucleotide-activated, nonselective cation channels, and across species from nematode to human

Cyclic-nucleotide-activated, nonselective cation channels have a central role in sensory transduction. They are most likely tetramers, composed of two subunits (α and β or 1 and 2), with the former, but not the latter, being able to form homomeric cyclic-nucleotide-activated channels. Identified members of this channel family now include, in vertebrates, the rod and cone channels mediating visual transduction and the channel mediating olfactory transduction, each apparently with distinct α- and β-subunits. Homologous channels have also been identified in Drosophila melanogaster and Caenorhabditis elegans. By co-expressing any combination of two α-subunits, or α- and β-subunits, of this channel family in HEK 293 cells, we have found that they can all co-assemble functionally with each other, including those from fly and nematode. This finding suggests that the subunit members so far identified form a remarkably homogeneous and conserved group, functionally and evolutionarily, with no subfamilies yet identified. The ability to cross-assemble allows these subunits to potentially generate a diversity of heteromeric channels, each with properties specifically suited to a particular cellular function.