The active Zot domain (aa 288–293) increases ZO‐1 and myosin 1C serine/threonine phosphorylation, alters interaction between ZO‐1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation
Bibliographic record
Abstract
Vibrio cholerae ‐derived zonula occludins toxin (Zot) is a multifunctional protein that reversibly disassembles intestinal tight junctions (tjs). Zot structure‐function analysis has mapped this activity to aa 288–293, named AT1002. AT1002 reduced transepithelial electrical resistance across rat small intestine, ex vivo, as did Zot and its processed mature form, ΔG. AT1002 increased in vivo permeability to sugar tracers, whereas scrambled control peptides did not. Binding and barrier assays in proteinase activated receptor (PAR) 2 ‐expressing and PAR 2 ‐null cells established AT1002 activity to be PAR 2 dependent. Coincident with the increased intestinal permeability, confocal microscopy of AT1002‐exposed rat intestinal IEC6 cells revealed displacement of ZO‐1 and occludin from intercellular boundaries. In coimmunoprecipitation assays, AT1002 decreased ZO‐1‐occludin and ZO‐1‐claudin 1 interactions coincident with PKCα‐dependent ZO‐1 serine/threonine phosphorylation. Further, AT1002 increased serine phosphorylation of myosin 1C and, at the same time, transiently diminished its association with ZO‐1. The COOH‐terminal domain of ZO‐1 was required for its association with myosin 1C. These data indicate that the NH 2 ‐terminal portion of active Zot contains a PAR 2 ‐activating motif, FCIGRL, that increases PKCα‐dependent ZO‐1 and myosin 1C serine/threonine phosphorylation. These modifications provoke selective disengagement of ZO‐1 from its binding partners, occludin, claudin 1, and myosin 1C, coincident with opening of tjs.—Goldblum, S. E., Rai, U., Tripathi, A., Thakar, M., De Leo, L., Di Toro, N., Not, T., Ramachandran, R., Puche, A. C., Hollenberg, M. D., Fasano, A. The active Zot domain (aa 288–293) increases ZO‐1 and myosin 1C serine/ threonine phosphorylation, alters interaction between ZO‐1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation. FASEB J. 25, 144–158 (2011). www.fasebj.org
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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 | 0.001 |
| 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".