TAPT1 interacts with SUCO to maintain the homeostasis of newly synthesized proteins and brain development in mice
Bibliographic record
Abstract
Genetic mutations in Tapt1 cause complex skeletal dysplasia and structural brain abnormalities. Although the pathogenesis underlying skeletal dysplasia has been explored, the functions and potential mechanisms of transmembrane anterior–posterior transition 1 (TAPT1) during brain development have not been reported. Here, we show that the brains of Tapt1 conditional knockout mice exhibit severe neurodevelopmental defects, including impaired proliferation and differentiation of neural progenitor cells and defects in dendritic and synaptic development, leading to severe microcephaly, motor dysfunction, and early death. Mechanically, we reveal that TAPT1 interacts with SUCO in the endoplasmic reticulum to maintain newly synthesized proteins, including those important for brain development. The TAPT1–SUCO complex plays an essential role in the homeostasis of newly synthesized proteins, and its loss causes overactivated protein degradation, as well as impaired endoplasmic reticulum-to-Golgi trafficking and organelle structures. Our results thus provide insights into the pathogenesis of TAPT1 and SUCO mutation–associated diseases that share similar pathologies.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".