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Record W4410118665 · doi:10.1038/s41467-025-59430-w

A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation

2025· article· en· W4410118665 on OpenAlexafffund
Patryk Poliński, Marta Miret-Cuesta, Alfonsa Zamora‐Moratalla, Federica Mantica, Gerard Cantero-Recasens, Miguel Sabariego-Navarro, Davide Normanno, L. Iñiguez, Cruz Morenilla‐Palao, Patricia Ordoño, Sophie Bonnal, Jonathan D. Ellis, Raúl Gómez, Hugo Fanlo-Ucar, María Martínez de Lagrán, Álvaro Fernández‐Blanco, Cristina Rodríguez-Marin, Jon Permanyer, Orsolya Fölsz, Eduardo Dominguez, Cèsar Sierra, Diana Legutko, José Wojnacki, Juan Luis Musoles Lleó, Maria Pia Cosma, Francisco José Muñoz, Benjamin J. Blencowe, Eloı́sa Herrera, Mara Dierssen, Manuel Irimia

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdvanced Fluorescence Microscopy Techniques
Canadian institutionsUniversity of Toronto
FundersAgencia Estatal de InvestigaciónCanadian Institutes of Health ResearchUniversity of TorontoAgència de Gestió d'Ajuts Universitaris i de RecercaNational Institutes of HealthGeneralitat de CatalunyaEuropean CommissionMinisterio de Ciencia e InnovaciónCentres de Recerca de Catalunya
KeywordsRHOAActinCell biologyDynamics (music)Actin cytoskeletonSignal transductionBiologyCytoskeletonGeneticsPhysicsCell

Abstract

fetched live from OpenAlex

Actin cytoskeleton dynamics is essential for proper nervous system development and function. A conserved set of neuronal-specific microexons influences multiple aspects of neurobiology; however, their roles in regulating the actin cytoskeleton are unknown. Here, we study a microexon in DAAM1, a formin-homology-2 (FH2) domain protein involved in actin reorganization. Microexon inclusion extends the linker region of the DAAM1 FH2 domain, altering actin polymerization. Genomic deletion of the microexon leads to neuritogenesis defects and increased calcium influx in differentiated neurons. Mice with this deletion exhibit postsynaptic defects, fewer immature dendritic spines, impaired long-term potentiation, and deficits in memory formation. These phenotypes are associated with increased RHOA/ROCK signaling, which regulates actin-cytoskeleton dynamics, and are partially rescued by treatment with a ROCK inhibitor. This study highlights the role of a conserved neuronal microexon in regulating actin dynamics and cognitive functioning.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.052
Threshold uncertainty score0.567

Codex and Gemma teacher scores by category

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 science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.007
GPT teacher head0.295
Teacher spread0.288 · 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 teacher head, 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

Citations8
Published2025
Admission routes2
Has abstractyes

Explore more

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