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Record W2966569611 · doi:10.1038/s41467-019-11425-0

Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export

2019· article· en· W2966569611 on OpenAlexafffund
Saskia Heybrock, Kristiina Kanerva, Ying Meng, Chris Ing, Anna Liang, Zi-Jian Xiong, Xialian Weng, Young Ah Kim, Richard F. Collins, William S. Trimble, Régis Pomès, Gilbert G. Privé, Wim Annaert, Michael Schwake, Jöerg Heeren, Renate Lüllmann‐Rauch, Sergio Grinstein, Elina Ikonen, Paul Säftig, Dante Neculai

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicLipid Membrane Structure and Behavior
Canadian institutionsSickKids FoundationPrincess Margaret Cancer CentreHospital for Sick ChildrenUniversity of Toronto
FundersNatural Science Foundation of Zhejiang ProvinceFonds Wetenschappelijk OnderzoekCanadian Institutes of Health ResearchKU LeuvenSuomen KulttuurirahastoNational Natural Science Foundation of ChinaAcademy of FinlandHämeen RahastoZhejiang UniversityDeutsche ForschungsgemeinschaftHelsingin Yliopisto
KeywordsCell biologyIntegral membrane proteinCholesterolChemistryMembrane proteinLysosomeMembraneBiochemistryBiologyEnzyme

Abstract

fetched live from OpenAlex

Abstract The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol − like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.

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 score0.001
Threshold uncertainty score0.003

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)0.0010.001

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 head0.013
GPT teacher head0.277
Teacher spread0.264 · 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

Citations162
Published2019
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicLipid Membrane Structure and BehaviorFrench-language works237,207