Myelin Basic Protein as a “PI(4,5)P<sub>2</sub>-Modulin”: A New Biological Function for a Major Central Nervous System Protein
Bibliographic record
Abstract
The 18.5 kDa isoform of myelin basic protein (MBP) is multifunctional and has previously been shown to have structural and phenomenological similarities with domains of other membrane- and cytoskeleton-associated proteins such as MARCKS (myristoylated alanine-rich C kinase substrate). Here, we have investigated whether 18.5 kDa MBP can sequester phosphatidylinositol-(4,5)-bis-phosphate (PI(4,5)P 2) in membranes, like MARCKS and other "PIPmodulins" do. Using fluorescence-quenching and electron paramagnetic resonance (EPR) spectroscopy, and model membranes containing BODIPY-FL- or proxyl-labeled PI(4,5)P 2, respectively, we have demonstrated that MBP laterally sequesters PI(4,5)P 2. The MBP-PI(4,5)P 2 interactions are electrostatic, partially cholesterol-dependent, and sensitive to phosphorylation, deimination, and Ca (2+)-CaM binding. Confocal microscopy of cultured oligodendrocytes also revealed patched colocalization of MBP and PI(4,5)P 2, indicating the spatial clustering of PI(4,5)P 2 in the plasma membrane. On the basis of these findings as well as the overwhelming convergence of functional properties, modifying enzymes, and interaction partners, we propose that MBP is mechanistically related to GAP-43, MARCKS, and CAP-23. During myelinogenesis, it may mediate calcium and phosphorylation-sensitive plasma membrane availability of PI(4,5)P 2. This regulation of PI(4,5)P 2 availability at the cell cortex may be coupled to the elaboration and outgrowth of the membranous cellular processes by oligodendrocytes.
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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 | 0.001 |
| 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".