The role of histidine residues in the pHı sensitivity of the Na+/H+ exchanger /
Bibliographic record
Abstract
Na+/H+ exchanger (NHE) is a major contributor in controlling intracellular pH. The activity of this protein is allosterically modified by intracellular H+. Histidine residues of the NHE that face the cytoplasm may be involved in determining the intracellular pH set point, with their state of protonation influencing the rate of Na +/H+ exchange. To test this hypothesis, histidine residues in the ubiquitously expressed NHE isoform (NHE1) that are relatively conserved amongst members of the NHE gene family were substituted by site-directed mutagenesis and the mutants were stably transfected into mammalian cells that are deficient in endogenous Na+/H + exchange activity. The pHi sensitivity of each mutant was evaluated by measuring the rate of 22Na + influx as a function of the intracellular H+ concentration. Mutation of the histidines located at the putative cytoplasmic face of the N-terminal transmembraneous domain of NHE1 did not show any significant effect on the pHi sensitivity of the protein. By contrast, substitution of histidines located in the C-terminal cytoplasmic tail activated the exchanger by increasing its sensitivity to H+. These mutants were no longer activated in response to protein kinase C, when compared to wild type. Taken together, these data support the hypothesis that some of the relatively conserved histidine residues in the C-terminal cytoplasmic tail of NHE1 may be involved in determining the pHi "threshold" or "set point" of the transporter.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".