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Record W4224242350 · doi:10.1038/s41467-022-29725-3

Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function

2022· article· en· W4224242350 on OpenAlexfundno aff
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Bo Ram Lee, Amy Lee, Johannes Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon channel regulation and function
Canadian institutionsnot available
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Eye InstituteNational Institute on AgingFundación Alfonso Martín EscuderoNational Cancer InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthMemorial Sloan-Kettering Cancer CenterYork University
KeywordsCell biologyT cellDepolarizationBiologyStimulationT-cell receptorPatch clampApoptosisMolecular biologyElectrophysiologyBiophysicsImmune systemImmunologyNeuroscienceBiochemistry

Abstract

fetched live from OpenAlex

Abstract TCR stimulation triggers Ca 2+ signals that are critical for T cell function and immunity. Several pore-forming α and auxiliary β subunits of voltage-gated Ca 2+ channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca 2+ signaling in T cells is controversial. We here identify Ca V β1, encoded by Cacnb1 , as a regulator of T cell function. Cacnb1 deletion enhances apoptosis and impairs the clonal expansion of T cells after lymphocytic choriomeningitis virus (LCMV) infection. By contrast, Cacnb1 is dispensable for T cell proliferation, cytokine production and Ca 2+ signaling. Using patch clamp electrophysiology and Ca 2+ recordings, we are unable to detect voltage-gated Ca 2+ currents or Ca 2+ influx in human and mouse T cells upon depolarization with or without prior TCR stimulation. mRNAs of several VGCC α1 subunits are detectable in human (Ca V 3.3, Ca V 3.2) and mouse (Ca V 2.1) T cells, but they lack transcription of many 5’ exons, likely resulting in N-terminally truncated and non-functional proteins. Our findings demonstrate that although Ca V β1 regulates T cell function, these effects are independent of VGCC channel activity.

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 score0.351
Threshold uncertainty score0.441

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 science0.0000.000
Research integrity0.0000.000
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 head0.012
GPT teacher head0.243
Teacher spread0.231 · 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

Citations39
Published2022
Admission routes1
Has abstractyes

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