Syntaxin 3 regulates apical membrane integrity in proximal tubule epithelial cells and prevents Fanconi syndrome development
Bibliographic record
Abstract
INTRODUCTION: Epithelial cell polarity is crucial for the proper functioning of various organs, including the kidneys. Syntaxin 3, a key molecule in membrane-vesicle fusion, is localized in the apical membrane of proximal tubule epithelial cells (PTECs). Although in vitro studies using the other type of epithelial cells besides PTECs have shown the role of syntaxin 3 in regulating apical membrane integrity, its function in epithelial cells in vivo, particularly in PTECs, remains undefined. METHODS: We analyzed the renal phenotypes of a newly generated PTEC-specific Stx3 knockout mice (Stx3-cKO) and examined urine samples from patients with microvillus inclusion disease (MVID) carrying STX3 mutations. RESULTS: Stx3-cKO mice exhibited features of Fanconi syndrome, including increased urinary excretion of phosphorus, glucose, amino acids, and low-molecular-weight proteins. Patients with MVID showed similar urinary abnormalities. The mice exhibited brush border atrophy and vesicle transport stagnation, as evidenced by electron microscopy, and increased subapical localization of trafficking markers, Rab11 and vesicle-associated membrane protein 8. Key transporters and receptors including sodium-dependent phosphate cotransporter type 2a, sodium-glucose cotransporter 2, a protein related to the neutral and basic amino acid transport protein rBAT, and megalin showed mislocalization and/or altered expression. Syntaxin 3 deficiency disrupted the apical expression of ezrin, a crucial protein that links the actin cytoskeleton to the plasma membrane. Both receptor-mediated and fluid-phase endocytosis were impaired in Stx3-cKO mice. CONCLUSIONS: Our results highlight the critical role of syntaxin 3 in maintaining PTEC function and apical polarity, providing new insights into the kidney manifestations of MVID and the molecular mechanisms underlying Fanconi syndrome.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".