title: TASK-5, a novel member of the tandem pore K+ channel family.
abstract: We have cloned a novel member of the tandem pore K+ channel family from human brain cDNA. The novel cDNA encodes a 330-residue polypeptide of predicted molecular mass 36 kDa. We have named the channel TASK-5 owing to its sequence homology with TASK-1 and TASK-3. TASK-5 mRNA is expressed in pancreas, liver, kidney, lung, ovary, testis and heart. However, expression of TASK-5 in heterologous systems failed to elicit ionic currents. Removal of a putative endoplasmic reticulum retention sequence did not alter this finding and the distribution of channel proteins in HEK293 cells was similar for both TASK-1 and TASK-5. We tested whether TASK-5 could form heteromers with TASK-1. We show a mutant form of TASK-1 (H98N) to have a radically reduced sensitivity to acidification. Proton sensitivity could be rescued by injecting equimolar amounts of wild-type and mutant TASK-1 cRNA into Xenopus oocytes; the effect was that expected if half the channels formed are heteromers. Co-expression of TASK-5 with TASK-1 H98N does not affect the proton sensitivity of mutant TASK-1; thus TASK-5 appears not to form heteromers with TASK-1. Nonetheless, TASK-5 may require some other, unidentified partner subunit to form functional channels in the plasma membrane or it may form a channel in an intracellular organelle.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, UK.
authors.forename: I
authors.initials: I
authors.lastname: Ashmole
authors.forename: P A
authors.initials: PA
authors.lastname: Goodwin
authors.forename: P R
authors.initials: PR
authors.lastname: Stanfield
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008164:Luminescent Proteins / Q000235:genetics; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D018076:DNA, Complementary; C431132:KCNK15 protein, human; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C420132:potassium channel subfamily K member 3