TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons
Bibliographic record
Abstract
Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these 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) | 0.000 | 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) | 0.000 | 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".