Narrowing the Rab GAP: identifying a role for TBC-2 in endosomal trafficking in «Caenorhabditis elegans»
Bibliographic record
Abstract
By controlling many steps of organelle biogenesis and cargo transport, Rab GTPases are central regulators of vesicular trafficking in endocytic and exocytic pathways. During endosomal maturation, coordinated activity of the early endosomal Rab5 and late endosomal Rab7 GTPases is required for a proper cargo delivery to the lysosome. It has been proposed that Rab5 induces Rab7 recruitment on vesicles, which in turn, induces Rab5 inactivation and removal. However, this Rab5 and Rab7 coupling model is incomplete without regulatory elements such as Rab GAPs to restrict their spatio-temporal overlap. In the present thesis, we have identified TBC-2, a conserved putative Rab GAP, as a regulator of endosome to lysosome trafficking in C .elegans. Our data show that TBC-2 localizes on late endosomes in a RAB-7 dependent manner. Consistent with the Rab conversion model, TBC-2 functions as a GAP to inactivate RAB-5 to facilitate early to late endosome transition. Furthermore, works from this thesis demonstrate that loss of tbc-2 perturbs the normal degradation of the yolk, a cholesterol binding/transport protein that has been suggested to serve as an energy source during development. Consistent with that, we observed that tbc-2 mutant L1 larvae die prematurely when hatched in absence of food. The exact function of yolk in C. elegans is not fully understood but our data suggest that yolk might be important for survival of starvation-induced L1 diapause in C. elegans. These studies highlight that a tight coordination between Rab GTPases and their regulators is essential for intracellular trafficking and alteration of this process causes detrimental effect on physiological function. They also underline that better understanding of mechanisms of vesicular transport is important for unravelling the etiology of trafficking diseases.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".