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Record W2593032425 · doi:10.1074/jbc.m117.775114

A forward genetic screen identifies a negative regulator of rapid Ca2+-dependent cell egress (MS1) in the intracellular parasite Toxoplasma gondii

2017· article· en· W2593032425 on OpenAlexaff
J. Michael McCoy, Rebecca J. Stewart, Alessandro D. Uboldi, Dongdi Li, Jan Schröder, Anthony T. Papenfuss, Adele M. Lehane, Leonard J. Foster, Christopher J. Tonkin

Bibliographic record

VenueJournal of Biological Chemistry · 2017
Typearticle
Languageen
FieldImmunology and Microbiology
TopicToxoplasma gondii Research Studies
Canadian institutionsUniversity of British Columbia
FundersNational Health and Medical Research CouncilAustralian Research Council
KeywordsToxoplasma gondiiBiologyCell biologyMutantCytosolKinaseMotilityGenetic screenIntracellularIntracellular parasiteMicronemeSignal transductionPhosphorylationRegulatorGliding motilityGeneApicomplexaGeneticsBiochemistryEnzymeAntibodyImmunology

Abstract

fetched live from OpenAlex

Toxoplasma gondii , like all apicomplexan parasites, uses Ca 2+ signaling pathways to activate gliding motility to power tissue dissemination and host cell invasion and egress. A group of "plant-like" Ca 2+ -dependent protein kinases (CDPKs) transduces cytosolic Ca 2+ flux into enzymatic activity, but how they function is poorly understood. To investigate how Ca 2+ signaling activates egress through CDPKs, we performed a forward genetic screen to isolate gain-of-function mutants from an egress-deficient cdpk3 knockout strain. We recovered mutants that regained the ability to egress from host cells that harbored mutations in the gene Suppressor of Ca 2+ -dependent Egress 1 (SCE1). Global phosphoproteomic analysis showed that SCE1 deletion restored many Δ cdpk3 -dependent phosphorylation events to near wild-type levels. We also show that CDPK3-dependent SCE1 phosphorylation is required to relieve its suppressive activity to potentiate egress. In summary, our work has uncovered a novel component and suppressor of Ca 2+ -dependent cell egress during Toxoplasma lytic growth.

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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.024
GPT teacher head0.276
Teacher spread0.252 · 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

Citations33
Published2017
Admission routes1
Has abstractyes

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