Impact of N‐linked glycans on the dual short fibulin/ <scp>LTBP</scp> ‐4 axes regulating elastogenesis
Bibliographic record
Abstract
Elastic fibers are key extracellular components, providing elasticity to blood vessels, lungs, skin, and bladder. Elastic fiber formation requires the accessory proteins fibulin-4, fibulin-5, and the long and short isoforms of the latent TGFβ binding protein-4 (LTBP-4L/S). We established two molecular axes, LTBP-4L/fibulin-4 and LTBP-4S/fibulin-5, defined similar and distinct functions, and determined the role of N-linked glycans in this context. Glycoproteomic analysis identified the specific N-linked glycans in these proteins. Biophysical analyses revealed that the N-linked glycans of LTBP-4L, but not fibulin-4, were critical for fibulin-4-mediated conformational extension of LTBP-4L, impacting its function and assembly. Biochemical and recombinant removal of N-linked glycans from fibulin-4 enhanced its interaction with tropoelastin and elastic fiber formation, indicating an inhibitory role for these N-glycans. Fibulin-5 strongly interacted with and robustly induced a conformational extension of LTBP-4S, leading to enhanced binding to fibronectin, increased LTBP-4S deposition, and doubling of elastic fiber formation. Loss of N-linked glycans from fibulin-5, but not LTBP-4S, reduced their interaction by about 10-fold and abolished the ability of fibulin-5 to extend LTBP-4S conformationally. The presence of fibulin-5-extended LTBP-4S did not trigger tropoelastin aggregation in an in vitro assembly assay but boosted elastic fiber-like assembly massively when fibulin-4 and LTBP-4L were additionally present, suggesting synergistic effects. N-linked glycans in fibulin-5 were essential in this process. The study uncovers novel mechanisms that regulate elastic fiber formation, including overlapping and distinct roles of the LTBP-4L/fibulin-4 and the LTBP-4S/fibulin-5 axes and the importance of N-linked glycans of each of these proteins.
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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".