Structural and Functional Changes in the C‐terminal Regulatory Tail of the Na+/H+ Exchanger Mediate Phosphorylation Induced Regulation
Bibliographic record
Abstract
The Na + /H + exchanger isoform 1 (NHE1) is a plasma membrane pH regulatory protein that removes one intracellular H+ in exchange for an extracellular Na+. NHE1 is inactive at alkaline intracellular pH but is active with decreasing pHi. The set point of the protein is altered by phosphorylation of the cytoplasmic tail. We examined the mechanism by which phosphorylation mediates NHE1 activation. In the full length protein, mutation of Ser 770 and Ser 771 to either Asp or Ala resulted in an inability to stimulate the protein by sustained intracellular acidosis. By using western blotting against the HA‐tagged full length NHE1 protein, we found that NHE1 proteins with the mutation S726/729D and S770/771A showed no difference in the digestion pattern or sensitivity to digestion compared with the wild type. However, the S770/771D mutant always appeared to be more sensitive to digestion with trypsin than controls. We examined the expressed C‐terminal regulatory region of NHE1 with and without phosphomimetic S770/771D mutations. These NHE1 proteins had varying sensitivity to trypsin digestion. This difference did not occur with phosphomimetic mutations at S703D, S726/729D. The results suggest that phosphorylation of NHE1 at Ser 770 and Ser 771 causes a significant changed in the conformation of the NHE1 regulatory tail that may affect NHE1 activity. Supported by Canadian Institutes of Health Research.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".