Disease relevance of TOK1

• Hypersensitivity to LiCl and improved growth in low K(+) are partly dependent on the Nha1p and Kha1p antiporters and on the Tok1p channel [1].

High impact information on TOK1

• Osmotic stress activates Hog1 MAP kinase, which phosphorylates at least two proteins located at the plasma membrane, the Nha1 Na+/H+ antiporter and the Tok1 potassium channel [2].
• Recently, external K1 toxin was shown to directly activate TOK1 channels in the plasma membranes of sensitive yeast cells, leading to excess potassium flux and cell death [3].
• Here, a mechanism by which killer cells resist their own toxin is shown: internal toxin inhibits TOK1 channels and suppresses activation by external toxin [3].
• K1 toxin acts in the absence of other viral or yeast products: toxin synthesized from a cDNA increases open probability of single TOK1 channels (via reversible destabilization of closed states) whether channels are studied in yeast cells or X. laevis oocytes [4].
• Random mutagenesis reveals a region important for gating of the yeast K+ channel Ykc1 [5].

Biological context of TOK1

• The current through TOK1 (YKC1), the outward-rectifying K+ channel in Saccharomyces cerevisiae, was amplified by expressing TOK1 from a plasmid driven by a strong constitutive promoter [6].
• This trk1Delta trk2Delta double mutant hyperexpressing the TOK1 transgene had a higher internal K+ content than one expressing the empty plasmid [6].
• We have shown that the presence of the Tok1 channel strongly influences membrane potential: deletion of the TOK1 gene results in significant plasma membrane depolarization, whereas strains overexpressing the TOK1 gene are hyperpolarized [7].
• Non-targeted mutagenesis studies of the yeast K(+) channel, TOK1, have led to identification of functional domains common to other cation channels as well as those so far not found in other channels [8].
• These and additional results indicate that external K+ acts as a ligand to inactivate the TOK1p channel, and they implicate a gating process mediated by a single cation binding site within the membrane electric field, but distinct from the permeation pathway [9].

Anatomical context of TOK1

• Physiological characterization of the yeast plasma membrane outward rectifying K+ channel, DUK1 (TOK1), in situ [10].
• We examined protoplasts of these TOK1-hyperexpressing cells under a patch clamp [6].
• Similar potassium currents were recorded from wildtype S. cerevisiae spheroplasts, but not from those in which the DUK1 locus had been disrupted [11].

Associations of TOK1 with chemical compounds

• In contrast, the nonanesthetic 1,2-dichlorohexafluorocyclobutane did not potentiate TOK1 currents in concentrations up to five times the MAC value predicted by the Meyer-Overton hypothesis based on oil/gas partition coefficients [12].
• RESULTS: Studies with two-electrode voltage clamp at room temperature showed that halothane, isoflurane, and desflurane increased TOK1 outward currents by 48-65% in barium Frog Ringer's perfusate [12].
• These PP mutations specifically caused marked defects in the 'C1' states, a set of interrelated closed states that Ykc1 enters and exits at rates of tens to hundreds of milliseconds [5].
• In the yeast potassium channel, Tok1p, the external ring of aspartate residues modulates both gating and conductance [13].
• Cells carrying the duk1 delta 1::HIS disruption in addition to a chimeric gene comprising DUK1 behind the GAL1 promoter showed outward currents when grown in galactose, but not when grown in glucose [11].

Other interactions of TOK1

• Characterization of potassium transport in wild-type and isogenic yeast strains carrying all combinations of trk1, trk2 and tok1 null mutations [14].
• Deletion mutants of the two unknown genes J0909 and J0911 are viable [15].

References