An orphan kinesin controls trypanosome morphology transitions by targeting FLAM3 to the flagellum
Bibliographic record
Abstract
Trypanosoma brucei undergoes life cycle form transitions from trypomastigotes to epimastigotes in the insect vector by re-positioning the mitochondrial genome and re-locating the flagellum and flagellum-associated cytoskeletal structures.The mechanism underlying these dramatic morphology transitions remains poorly understood.Here we report the regulatory role of the orphan kinesin KIN-E in controlling trypanosome morphology transitions.KIN-E localizes to the flagellum and is enriched at the flagellar tip, and this localization depends on the C-terminal m-calpain domain III-like domains.Depletion of KIN-E in the trypomastigote form of T. brucei causes major morphology changes and a gradual increase in the level of EP procyclin, generating epimastigote-like cells.Mechanistically, through its C-terminal importin α-like domain, KIN-E targets FLAM3, a flagellar protein involved in morphology transitions, to the flagellum to promote elongation of the flagellum attachment zone and positioning of the flagellum and flagellum-associated cytoskeletal structure, thereby maintaining trypomastigote cell morphology.Our findings suggest that morphology transitions in trypanosomes require KIN-E-mediated transport of FLAM3 to the flagellum. Author summaryTrypanosoma brucei, the causative agent of sleeping sickness in humans and nagana in cattle in sub-Saharan Africa, has a complex life cycle by alternating between the tsetse fly vector and the mammalian hosts.In the gut of tsetse flies, trypanosomes undergo life cycle transitions from the trypomastigote form to the epimastigote form by re-positioning the mitochondrial genome and re-locating the flagellum and flagellum-associated cytoskeletal structures.Previous work demonstrated that elongation of the flagellum attachment zone plays an important role in controlling morphology transitions, but how it is regulated remains poorly understood.This work discovered that an orphan kinesin plays an essential role in regulating trypanosome morphology transitions.This novel kinesin localizes to the flagellum and targets FLAM3, one of the two flagellar proteins involved in morphology transitions, to the flagellum.This work suggests that trypanosome morphology transitions require kinesin-mediated transport of FLAM3 to the flagellum to promote the
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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) | 0.001 | 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".