Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting
Bibliographic record
Abstract
SUMMARY Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia and can be impaired in human diseases. Maintenance of apical polarity in the face of CFTR non-polarized delivery and compromised apical retention of mutant CFTRs lacking PDZ-domain protein (NHERF1) interaction, remains enigmatic. Here we show that basolateral CFTR delivery originates from biosynthetic (~35%) and endocytic (~65%) recycling missorting. Basolateral channels are retrieved via basolateral-to-apical transcytosis, enhancing CFTR apical expression by two-fold and suppressing its degradation. CFTR transcytosis is microtubule-dependent but independent of Myo5B-, Rab11- and NHERF1 binding to its C-terminal DTRL motif in airway epithelia. Increased basolateral delivery due to compromised apical recycling and accelerated internalization upon impaired NHERF1-CFTR association is largely counterbalanced by CFTR efficient basolateral internalization and apical transcytosis. Thus, transcytosis represents a previously unrecognized but indispensable mechanism for maintaining CFTR apical polarity by attenuating its constitutive and mutation-induced basolateral missorting.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".