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Record W4413472568 · doi:10.1101/2025.08.21.671625

α-catenin phosphorylation is actomyosin-sensitive and required for epithelial barrier functions through Afadin

2025· preprint· en· W4413472568 on OpenAlexafffund
Jeanne M. Quinn, Phuong M. Le, Anthea Weng, Annette S. Flozak, Stephen Sai Folmsbee, Erik Arroyo-Colon, Mitsuhiko Ikura, Noboru Ishiyama, Cara J. Gottardi

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSkin and Cellular Biology Research
Canadian institutionsPrincess Margaret Cancer CentreUniversity of Toronto
FundersNational Center for Research ResourcesNational Cancer InstituteNational Eye InstituteTokyo Metropolitan UniversityNational Heart, Lung, and Blood InstitutePrincess Margaret Cancer FoundationNorthwestern University
KeywordsCateninPhosphorylationChemistryCell biologyBiophysicsBiologySignal transductionWnt signaling pathway

Abstract

fetched live from OpenAlex

Zonula adherens junctions (zAJ) are spatially proximal to tight junctions (TJ), in a superstructure known as the apical junctional complex (AJC). A key component of the AJC is a circumferential ring of filamentous (F)-actin, but how actomyosin contractility drives AJC structure and epithelial barrier function is incompletely understood. Here, we show that a central mechanosensitive component of zAJ, α-catenin (α-cat), undergoes force-dependent phosphorylation in an unstructured linker region. This modification in turn primes the α-cat mechanosensitive Middle-region for effector-binding. We credential Afadin, a multi-domain TJ/AJ scaffold protein, as mechano-chemical binding partner of α-cat, identifying residues in α-cat required for this interaction. α-cat phosphorylation and Afadin-binding are required for their co-enrichment at zAJ and epithelial barrier function. A mouse model that prevents α-cat phosphorylation is particularly detrimental to post-natal brain development. These data support a stepwise model where α-cat integrates mechanical and chemical signals to progressively promote zAJ enrichment, effector recruitment and epithelial barrier function.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.017
GPT teacher head0.258
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicSkin and Cellular Biology ResearchFrench-language works237,207