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Oligomerization of Equilibrative Nucleoside Transporter 1

2015· article· en· W3177137678 on OpenAlexaffabout
Xenia Cravetchi, Gonzalo L. Vilas, James R. Hammond

Bibliographic record

VenueThe FASEB Journal · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdenosine and Purinergic Signaling
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsNucleosideTransporterChemistryTransfectionOligomerColocalizationImmunoprecipitationBiochemistryHEK 293 cellsMolecular biologyBiologyGene

Abstract

fetched live from OpenAlex

Equilibrative nucleoside transporter 1 (ENT1) is a ubiquitously expressed membrane transporter in mammalian cells responsible for the transmembrane flux of endogenous nucleosides such as adenosine, as well as, chemotherapeutic, anti‐vial, and anti‐parasitic nucleoside analogues . The present study was designed to assess whether ENT1, like many other solute transporters, functions as a dimer or higher order oligomer. Previous functional studies from our laboratory suggested the presence of two populations of ENT1 with differential sensitivities to sulfhydryl reagents at the plasma membrane. Studies of ENT1 photoaffinity labelled membranes revealed multiple molecular mass bands on denaturing gels. Non‐denaturing Blue Native PAGE resulted in a molecular mass of ENT1 of 137 kDa (versus 55kDa monomer) suggesting a higher order oligomer or association with other proteins. Co‐immunoprecipitation studies on HEK293 cells expressing MYC‐ and HA‐hENT1 indicated that hENT1 can oligomerize. This was confirmed by immunofluorescence experiments, which showed a 1.5‐fold increase in colocalization of MYC‐hENT1 and HA‐hENT1 signal when the amount of transfected HA‐hENT1 cDNA was gradually increased while MYC‐hENT1 was kept constant in HEK293 cells. Finally, proximity ligation assays, performed on WT‐hENT1‐PK15 cells transiently transfected with MYC‐hENT1, showed interaction between the two pools of hENT1. These data support the hypothesis that ENT1 exists in the plasma membrane as a dimer, and possibly higher level protein complexes. Further work regarding the identity of the ENT1 complex components as well as the impact of these interactions on the function and inhibitor/substrate association with ENT1 remains to be determined. Supported by the Natural Science and Engineering Research Council of Canada.

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 score0.005

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.023
GPT teacher head0.251
Teacher spread0.228 · 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
Published2015
Admission routes2
Has abstractyes

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