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Record W2948557789 · doi:10.3389/fcell.2019.00113

The Lysosome Signaling Platform: Adapting With the Times

2019· review· en· W2948557789 on OpenAlex
Subothan Inpanathan, Roberto J. Botelho

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.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueFrontiers in Cell and Developmental Biology · 2019
Typereview
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsToronto Metropolitan University
FundersCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsRyerson University
KeywordsLysosomeAutophagyCell biologymTORC1ATG16L1EndocytosisCellular adaptationBiologyTFEBOrganelleSignal transductionCellBiochemistryPI3K/AKT/mTOR pathway

Abstract

fetched live from OpenAlex

Lysosomes are the terminal degradative compartment of autophagy, endocytosis and phagocytosis. What once was viewed as a simple acidic organelle in charge of macromolecular digestion has emerged as a dynamic organelle capable of integrating cellular signals and producing signal outputs. In this review, we focus on the concept that the lysosome surface serves as a platform to assemble major signaling hubs like mTORC1, AMPK, GSK3 and the inflammasome. These molecular assemblies integrate and facilitate cross-talk between signals such as amino acid and energy levels, membrane damage and infection, and ultimately enable responses such as autophagy, cell growth, membrane repair and microbe clearance. In particular, we review how molecular machinery like the vacuolar-ATPase proton pump, sestrins, the GATOR complexes, and the Ragulator, modulate mTORC1, AMPK, GSK3 and inflammation. We then elaborate how these signals control autophagy initiation and resolution, TFEB-mediated lysosome adaptation, lysosome remodeling, antigen presentation, inflammation, membrane damage repair and clearance. Overall, by being at the cross-roads for several membrane pathways, lysosomes have emerged as the ideal surveillance compartment to sense, integrate and elicit cellular behavior and adaptation in response to changing environmental and cellular conditions.

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: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.992
Threshold uncertainty score0.504

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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)0.0000.000

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 head0.028
GPT teacher head0.277
Teacher spread0.248 · 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