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Record W4405676731 · doi:10.1101/2024.12.19.629437

Segregated localization of target-SNARE proteins within presynaptic terminals of Munc18-1 deficient photoreceptors

2024· preprint· en· W4405676731 on OpenAlexafffund
Mengjia Huang, Chun Hin Chow, Jason Charish, Karen Indrawinata, Hidekiyo Harada, Valerie A. Wallace, Philippe P. Monnier, Shuzo Sugita

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCellular transport and secretion
Canadian institutionsUniversity of TorontoUniversity Health Network
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchHospital for Sick ChildrenUniversity of Texas Southwestern Medical Center
KeywordsExocytosisCell biologySyntaxinBiologySNARE complexSynaptic vesicleVesicular Transport ProteinsMunc-18SynapseNeuroscienceVesicleMembraneVacuoleBiochemistryCytoplasm

Abstract

fetched live from OpenAlex

Abstract Sec1/Munc18 family proteins are essential for SNARE-mediated vesicular exocytosis. However, where SNARE proteins are localized in Munc18-1 deficient presynaptic terminals remains unclear due to the rapid degeneration of neurons lacking Munc18-1. Here, we found that removing Munc18-1 from photoreceptor cells did not result in major cellular loss until postnatal day 14, which allowed us to investigate the role of Munc18-1 in endogenous presynaptic terminals. In the absence of Munc18-1, even before major photoreceptor cell degeneration, functional impairments were present. While Munc18-1 was not required for the pre-synaptic enrichment of the t-SNARE proteins syntaxin-3 and SNAP-25, it played a critical role in their proper localization. In wild-type conditions, t-SNAREs are highly colocalized. However, in the absence of Munc18-1, their distribution becomes strikingly segregated. Immuno-electron microscopy revealed that without Munc18-1, syntaxin-3 is retained within various organelle membranes rather than being targeted to synaptic plasma membranes. These findings provide the first evidence that Munc18-1 is important to prevent segregation of syntaxin-3 and SNAP-25 within presynaptic terminals.

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 score0.004

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 head0.008
GPT teacher head0.204
Teacher spread0.196 · 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

Citations1
Published2024
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicCellular transport and secretion→French-language works237,207→