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Record W4410221777 · doi:10.1016/j.jbc.2025.110222

Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting

2025· article· en· W4410221777 on OpenAlexaboutno aff
Jan Dominik Speidel, Kaikai Yu, Ralph T. Böttcher

Bibliographic record

VenueJournal of Biological Chemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsnot available
FundersMax-Planck-GesellschaftDeutsche Forschungsgemeinschaft
KeywordsPhosphorylationLabrador RetrieverCell biologyChemistrySortingBiochemistryBiologyComputer scienceMedicinePathology

Abstract

fetched live from OpenAlex

Sorting nexin 17 (SNX17) functions as cargo receptor on endosomal membranes that enables the recycling of numerous membrane cargo proteins by binding to the Retriever complex. Yet, little is known how SNX17 activity or its membrane recruitment is regulated. Here, we report that phosphorylation of SNX17 at serine 38 (Ser38) within the phox domain serves as a critical regulatory switch governing its endosomal localization and function. A mutant form mimicking the phosphorylated state disrupts SNX17's ability to bind phosphatidylinositol-3-phosphate, which in turn impairs its association with early endosomal membranes and inactivates SNX17-dependent cargo-recycling in cells. Furthermore, our results demonstrate that Ser38 is part of an autoinhibitory mechanism to regulate SNX17 cargo binding. Collectively, these findings provide new insights into the dynamic regulation of SNX17 activity and Retriever-mediated sorting processes. It also highlights SNX17 Ser38 phosphorylation as a critical regulatory mechanism that controls SNX17's endosomal localization and cargo recycling function.

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 score0.003
Threshold uncertainty score0.012

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)0.0030.000

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 head0.010
GPT teacher head0.289
Teacher spread0.279 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

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