title: Genetic basis of tetrodotoxin resistance in pufferfishes.
abstract: Tetrodotoxin (TTX) is a highly potent neurotoxin that selectively binds to the outer vestibule of voltage-gated sodium channels. Pufferfishes accumulate extremely high concentrations of TTX without any adverse effect. A nonaromatic amino acid (Asn) residue present in domain I of the pufferfish, Takifugu pardalis, Na v1.4 channel has been implicated in the TTX resistance of pufferfishes . However, the effect of this residue on TTX sensitivity has not been investigated, and it is not known if this residue is conserved in all pufferfishes. We have investigated the genetic basis of TTX resistance in pufferfishes by comparing the sodium channels from two pufferfishes (Takifugu rubripes [fugu] and Tetraodon nigroviridis) and the TTX-sensitive zebrafish. Although all three fishes contain duplicate copies of Na v1.4 channels (Na v1.4a and Na v1.4b), several substitutions were found in the TTX binding outer vestibule of the two pufferfish channels. Electrophysiological studies showed that the nonaromatic residue (Asn in fugu and Cys in Tetraodon) in domain I of Na v1.4a channels confers TTX resistance. The Glu-to-Asp mutation in domain II of Tetraodon channel Na v1.4b is similar to that in the saxitoxin- and TTX-resistant Na+ channels of softshell clams . Besides helping to deter predators, TTX resistance enables pufferfishes to selectively feed on TTX-bearing organisms.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673, Singapore.
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
authors.forename: Song Qing
authors.initials: SQ
authors.lastname: Lu
authors.forename: Nidhi
authors.initials: N
authors.lastname: Dandona
authors.forename: Shean Long
authors.initials: SL
authors.lastname: See
authors.forename: Sydney
authors.initials: S
authors.lastname: Brenner
authors.forename: Tuck Wah
authors.initials: TW
authors.lastname: Soong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D017931:DNA Primers; D004351:Drug Resistance / Q000235:genetics*; D004594:Electrophysiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D023741:Takifugu / Q000235:genetics*; D013779:Tetrodotoxin / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; D015222:Sodium Channels; D013779:Tetrodotoxin