Differential processing and sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons
Bibliographic record
Abstract
We have examined the biosynthesis, post-translational processing and sorting of neurotrophins in both constitutive and regulated cells infected with a pro-NGF, pro-BDNF and/or pro-NT-3 encoding vaccinia virus. Our results show that: (1) pro-BDNF is generated as a 32 kDa precursor that is N-glycosylated and glyco-sulfated in its prodomain. The precursor undergoes N-terminal cleavage to generate mature BDNF (14 kDa) as well as a truncated form of the precursor (28 kDa). (2) Both 32 and 28 kDa BDNF are released into media and are able to stimulate TrkB auto-phosphorylation. (3) The production of 28 kDa BDNF, unlike that of mature BDNF, occurs in the ER and is generated by a novel enzyme called subtilisin/kexin isozyme-1 (SKI-1) at the RGLT 57↓SL site. (4) Results obtained from pulse-chase experiments, secretagogue-induced release, and immunocytochemistry suggest that, NGF and NT-3 are primarily secreted constitutively while BDNF is principally directed to the regulated secretory pathway. (5) In contrast to homodimeric NT-3, NT-3/BDNF heterodimer is primarily sorted to the regulated secretory pathway suggesting that for the NT-3/BDNF heterodimer, the presence of a single pro-BDNF chain is sufficient for packaging into large dense-core secretory vesicles and subsequent regulated release. (6) Blocking furin activity in AtT-20 cells with alpha1-PDX as well as increasing the level of expression of NGF and NT-3 precursors partially directed them into the regulated secretory pathway. Therefore, neurotrophins can be sorted into either the constitutive or regulated secretory pathways, and sorting may be regulated by the efficiency of furin cleavage in the TGN. This mechanism may explain how neuron-generated neurotrophins can act both as survival factors and as neuropeptides.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 teacher head, 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".