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Record W4289711886 · doi:10.1101/2022.08.02.502487

Coupling of protein condensates to ordered lipid domains determines functional membrane organization

2022· preprint· en· W4289711886 on OpenAlexafffund
Hongyin Wang, Sze Ham Chan, Simli Dey, Ivan Castello-Serrano, Jonathon A. Ditlev, Michael K. Rosen, Kandice R. Levental, Ilya Levental

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmune Response and Inflammation
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersNational Institute of General Medical SciencesNational Institutes of HealthVolkswagen FoundationHospital for Sick ChildrenWelch FoundationHoward Hughes Medical Institute
KeywordsLipid raftMembraneLipid microdomainSignal transducing adaptor proteinBiophysicsTransmembrane proteinChemistryLipid bilayerCell biologyCoupling (piping)Signal transductionReceptorBiologyBiochemistryMaterials science

Abstract

fetched live from OpenAlex

ABSTRACT During T-cell activation, the transmembrane adaptor Linker of Activation of T-cells (LAT) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains. However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T-cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation. Correspondingly, activation of T-cells induces protein condensates that associate with and stabilize raft-like membrane domains. Inversely, lipid domains nucleate and stabilize LAT protein condensates in both reconstituted and living systems. This coupling of lipid and protein assembly is functionally important, since uncoupling of lipid domains from cytoplasmic protein condensates abrogates T-cell activation. Thus, thermodynamic coupling between protein condensates and ordered lipid domains regulates the functional organization of living membranes. SUMMARY Membrane-associated protein condensates couple to ordered membrane domains to determine the functional organization of T-cell plasma membranes

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
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 score0.022
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.011
GPT teacher head0.204
Teacher spread0.193 · 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.

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

Citations29
Published2022
Admission routes2
Has abstractyes

Explore more

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