title: A divergent CFTR homologue: highly regulated salt transport in the euryhaline teleost F. heteroclitus.
abstract: The killifish, Fundulus heteroclitus, is a euryhaline teleost fish capable of adapting rapidly to transfer from freshwater (FW) to four times seawater (SW). To investigate osmoregulation at a molecular level, a 5.7-kilobase cDNA homologous to human cystic fibrosis transmembrane conductance regulator (hCFTR) was isolated from a gill cDNA library from SW-adapted killifish. This cDNA encodes a protein product (kfCFTR) that is 59% identical to hCFTR, the most divergent form of CFTR characterized to date. Expression of kfCFTR in Xenopus oocytes generated adenosine 3',5'-cyclic monophosphate-activated, Cl(-)-selective currents similar to those generated by hCFTR. In SW-adapted killifish, kfCFTR was expressed at high levels in the gill, opercular epithelium, and intestine. After abrupt exposure of FW-adapted killifish to SW, kfCFTR expression in the gill increased severalfold, suggesting a role for kfCFTR in salinity adaptation. Under similar conditions, plasma Na+ levels rose significantly after 8 h and then fell, although it is not known whether these changes are directly responsible for the changes in kfCFTR expression. The killifish provides a unique opportunity to understand teleost osmoregulation and the role of CFTR.
authors.affiliation: Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, University of Oxford, United Kingdom.
authors.forename: T D
authors.initials: TD
authors.lastname: Singer
authors.forename: S J
authors.initials: SJ
authors.lastname: Tucker
authors.forename: W S
authors.initials: WS
authors.lastname: Marshall
authors.forename: C F
authors.initials: CF
authors.lastname: Higgins
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007695:Killifishes; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014882:Water-Electrolyte Balance; D014981:Xenopus
chemical_list: C505032:CFTR protein, human; D015220:Calcium Channels; D018076:DNA, Complementary; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP