Classical 18.5‐and 21.5‐kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms
Bibliographic record
Abstract
The myelin basic protein (MBP) family arises from different transcription start sites of the golli (gene of oligodendrocyte lineage) complex, with further variety generated by differential splicing. The "classical" MBP isoforms are peripheral membrane proteins that facilitate compaction of the mature myelin sheath but also have multiple protein interactions. The early developmental golli isoforms have previously been shown to promote process extension and enhance Ca(2+) influx into primary and immortalized oligodendrocyte cell lines. Here, we have performed similar studies with the classical 18.5- and 21.5-kDa isoforms of MBP. In contrast to golli proteins, overexpression of classical MBP isoforms significantly reduces Ca(2+) influx in the oligodendrocyte cell line N19 as well as in primary cultures of oligodendroglial progenitor cells. Pharmacological experiments demonstrate that this effect is mediated by voltage-operated Ca(2+) channels (VOCCs) and not by ligand-gated Ca(2+) channels or Ca(2+) release from intracellular stores. The pseudo-deiminated 18.5-kDa and the full-length 21.5-kDa isoforms do not reduce Ca(2+) influx as much as the unmodified 18.5-kDa isoform. However, more efficient membrane localization (of overexpressed, pseudo-deiminated 18.5-kDa and 21.5-kDa isoforms of classical MBP containing the 21-nt 3'-untranslated region transit signal) further reduces the Ca(2+) response after plasma membrane depolarization, suggesting that binding of classical MBP isoforms to the plasma membrane is important for modulation of Ca(2+) homeostasis. Furthermore, we have found that the mature 18.5-kDa isoform expressed in oligodendrocytes colocalizes with VOCCs, particularly at the leading edge of extending membrane processes. In summary, our findings suggest a key role for classical MBP proteins in regulating voltage-gated Ca(2+) channels at the plasma membrane of oligodendroglial cells and thus also in regulation of multiple developmental stages in this cell lineage.
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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 | 0.001 |
| 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".