Regulation of the Epithelial Na<sup>+</sup> /H<sup>+</sup> Exchanger Isoform by the Cytoskeleton
Bibliographic record
Abstract
Members of the Na(+)/H(+) exchanger (NHE) family mediate electroneutral countertransport of H(+) for Na(+) across cellular membranes. The six known isoforms mediate transepithelial Na(+) transport processes and housekeeping functions such as the regulation of cellular and organellar pH and volume. NHE3 is found primarily in the apical membrane of epithelial cells of the kidney and gastrointestinal tract, where it mediates Na(+) (re)absorption. Its fine regulation, whether by hormones that utilize cAMP as a signalling mechanism, or by physical parameters such as the cell volume, provides the adjustments necessary for the maintenance of systemic salt and fluid balance. Although the exact molecular mechanism of this control is unknown, two major modes of regulation have been invoked: 1) alteration of the number of cell surface transporters by changes in the rate of endocytosis and/or exocytosis and 2) regulation of the intrinsic activity of the individual exchangers. NHE3 requires an intact cytoskeleton for its optimal function. Pharmacological interference with actin polymerization or myosin phosphorylation markedly inhibits the exchanger, without altering the number of transporters exposed at the surface. This effect is isoform specific and is mediated by the cytoplasmic tail of the transporter. The small GTP-binding protein, RhoA and its downstream effector, Rho kinase regulate NHE3, possibly by controlling the level of myosin phosphorylation, that in turn determines the organization of actin. The cytoskeleton may not only be involved in the maintenance of the basal rate of transport, but is also likely to sense physical alterations and transmit signals to modulate NHE3 activity, thus providing fast and effective control of the exchanger.
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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) | 0.002 | 0.001 |
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".