The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells
Bibliographic record
Abstract
Two CEACAM1 isoforms with different cytoplasmic domains, CEACAM1-L and CEACAM1-S, are unequally distributed in polarized epithelial MDCK cells. CEACAM1-S is exclusively apical whereas CEACAM1-L occurs both in apical and lateral cell surfaces. Using confocal microscopy and CEACAM1-L mutants, we identified several amino acids in the cytoplasmic domain that were instrumental for the lateral localization. Tyr515, but not Tyr488, constituted a prominent lateral targeting signal. Pervanadate-stimulated Tyr phosphorylation induced rapid phosphatidylinositol 3-kinase-dependent disappearance of lateral CEACAM1-L, whereas staurosporine, a Ser/Thr kinase inhibitor, resulted in slower phosphatidylinositol 3-kinase-independent disappearance. Both drugs caused accumulation of CEACAM1-L in a late endosome/lysosome compartment. Colocalization studies of occludin, ZO-1, E-cadherin, beta-catenin and desmoplakin indicated that laterally localized CEACAM1-L was present in adherens junctions but not in tight junctions or desmosomes. Overexpressed CEACAM1-L did not affect the organization of tight junction or adherens junction proteins, but perturbed the arrangement of desmosomes. The abundance of desmosomes in the lateral cell surfaces decreased significantly and the submembraneous cytokeratin filaments became disorganized. The signal for desmosomal perturbance resided within amino acids 484-518 in the C-terminal part of the cytoplasmic domain, among which an intact Tyr515 was indispensable.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".