Dimerization of the plasma membrane Na <sup>+</sup> /H <sup>+</sup> exchanger type 3 (NHE3)
Bibliographic record
Abstract
Many transmembrane transport proteins are known or inferred to function as homo or hetero oligomers. NHE3 has been reported to associate in oligomers. However, the direct NHE3‐NHE3 interaction, the oligomer configuration and the significance of oligomerization for NHE3 function and regulation are unknown. Using split‐ubiquitin yeast two‐hybrid system for membrane protein‐protein interactions and co‐immunoprecipitation in mammalian cells, we demonstrated that full‐length NHE3, its C‐terminal truncations, but not full‐length NHE1, interact with full‐length NHE3 prey and NHE3 exists as an oligomer in mammalian cells. We confirmed that NHE3 is a dimer on the plasma membrane by counting photobleaching steps in total internal reflection fluorescence images of NHE3‐mGFP expressed in NHE‐null cells. In its native state in opossum kidney cells, NHE3 exhibits highly cooperative Na + kinetics compatible with two substrate binding sites. To show functional cross‐talk between two NHE3 molecules in a dimer we used two NHE3 mutants: S552A/S605G (abolished regulation by protein kinase A, PKA) and E213I (transport defective). The transport activity of NHE‐null cells expressing S552A/S605G NHE3 mutant was comparable to wild‐type NHE3, but it was not affected by PKA activation. Co‐expression of both S552A/S605G and E213I NHE3 mutants restored the exchanger activity along with the PKA regulation. These findings suggest that NHE3 is present at the plasma membrane as homo dimers and NHE3 dimers may constitute the functional units of the transport and affect its regulation.
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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 | 0.000 | 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) | 0.000 | 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".