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Record W3122951897 · doi:10.1016/j.isci.2021.102076

The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor

2021· article· en· W3122951897 on OpenAlex
Toshimasa Takahashi, Yibin Huang, Kōichi Yamamoto, Go Hamano, Akemi Kakino, Fei Kang, Yuki Imaizumi, Hikari Takeshita, Yoichi Nozato, Satoko Nozato, Serina Yokoyama, Motonori Nagasawa, Tatsuo Kawai, Masao Takeda, Taku Fujimoto, Kazuhiro Hongyo, Futoshi Nakagami, Hiroshi Akasaka, Yoichi Takami, Yasushi Takeya, Ken Sugimoto, Herbert Y. Gaisano, Tatsuya Sawamura, Hiromi Rakugi

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueiScience · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAtherosclerosis and Cardiovascular Diseases
Canadian institutionsUniversity of Toronto
FundersJapan Society for the Promotion of Science
KeywordsInternalizationEndocytosisCell biologyArrestinG protein-coupled receptorReceptorReceptor-mediated endocytosisAngiotensin II receptor type 1ChemistryEndocytic cycleAngiotensin IIClathrinChinese hamster ovary cellBiologySignal transductionBiochemistry

Abstract

fetched live from OpenAlex

Arrestin-dependent activation of a G-protein-coupled receptor (GPCR) triggers endocytotic internalization of the receptor complex. We analyzed the interaction between the pattern recognition receptor (PRR) lectin-like oxidized low-density lipoprotein (oxLDL) receptor (LOX-1) and the GPCR angiotensin II type 1 receptor (AT1) to report a hitherto unidentified mechanism whereby internalization of the GPCR mediates cellular endocytosis of the PRR ligand. Using genetically modified Chinese hamster ovary cells, we found that oxLDL activates Gαi but not the Gαq pathway of AT1 in the presence of LOX-1. Endocytosis of the oxLDL-LOX-1 complex through the AT1-β-arrestin pathway was demonstrated by real-time imaging of the membrane dynamics of LOX-1 and visualization of endocytosis of oxLDL. Finally, this endocytotic pathway involving GPCR kinases (GRKs), β-arrestin, and clathrin is relevant in accumulating oxLDL in human vascular endothelial cells. Together, our findings indicate that oxLDL activates selective G proteins and β-arrestin-dependent internalization of AT1, whereby the oxLDL-LOX-1 complex undergoes endocytosis.

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.

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 score0.037
Threshold uncertainty score0.349

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 studies0.0000.001
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 head0.014
GPT teacher head0.220
Teacher spread0.206 · 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