The Lysosomal trafficking of prosaposin /
Bibliographic record
Abstract
Prosaposin is a 65 kDa glycoprotein that can either be targeted to the lysosomal compartment or further glycosylated to a 70 kDa form and secreted from the cell. In the lysosome, prosaposin is cleaved into four individual proteins known as saposins A, B, C and D that function as activators of sphingolipid degradation. Most soluble lysosomal proteins use the mannose 6-phophate receptor to traffic to the lysosome. However, several proteins including prosaposin have been shown not to use this mechanism. Since prosaposin binds several types of sphingolipids and that lipids are involved in the trafficking of proteins to various cellular destinations, we tested the hypothesis that these lipids mediate the trafficking of prosaposin to the lysosomes. Using inhibitors of sphingolipid synthesis in conjunction with mutagenic analysis and dominant negative competition with chimeric constructs, we demonstrated that the D functional domain of prosaposin interacts with sphingomyelin and that the carboxy-terminal region of prosaposin binds a sorting receptor. We also demonstrated that prosaposin binds to sortilin, a recently identified lysosomal sorting receptor. In conclusion, our research unfolded a novel mechanism of lysosomal transport involving a protein-lipid interaction and the sorting receptor sortilin.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".