Identification and experimental verification of a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels.
Studies of bacterial ion channels have provided significant insights into the structure-function relationships of mechanosensitive and voltage-gated ion channels. However, to date, very few bacterial channels that respond to small molecules have been identified, cloned, and characterized. Here, we use bioinformatics to identify a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels containing a channel domain related by sequence homology to the mechanosensitive channel of small conductance (MscS). In this initial report, we clone selected members of this channel family, use electrophysiological measurements to verify their ability to directly gate in response to cyclic nucleotides, and use osmotic downshock to demonstrate their lack of mechanosensitivity. In addition to providing insight into bacterial physiology, these channels will provide researchers with a useful model system to investigate the role of ligand-gated ion channels (LGICs) in the signaling processes of higher organisms. The identification of these channels provides a foundation for structural and functional studies of LGICs that would be difficult to perform on mammalian channels. Moreover, the discovery of bCNG channels implies that bacteria have cyclic nucleotide-gated and cyclic nucleotide-modulated ion channels, which are analogous to the ion channels involved in eukaryotic secondary messenger signaling pathways.
Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130, USA.
David B
DB
Caldwell
Hannah R
HR
Malcolm
Donald E
DE
Elmore
Joshua A
JA
Maurer
D000595:Amino Acid Sequence; D001419:Bacteria / Q000378:metabolism*; D003001:Cloning, Molecular; D019295:Computational Biology; D017124:Conserved Sequence; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D016680:Genome, Bacterial; D008969:Molecular Sequence Data
D054815:Cyclic Nucleotide-Gated Cation Channels