Antigen-induced reorientation of the microtubule organizing centre to the B cell immune synapse requires Rap activation and actin dynamics (IRM8P.704)
Bibliographic record
Abstract
Abstract B cell activation can be initiated by antigen presenting cells (APC) that display intact antigen (Ag) on their surface. Reorientation of the B cell microtubule-organizing centre (MTOC) towards the APC facilitates Ag internalization at the immune synapse (IS), which is critical for B cells to present Ag to T cells and elicit T cell help. We showed previously that BCR-induced activation of the Rap GTPase, a key regulator of cell polarity and actin dynamics, is required for IS formation. We now show that BCR-induced Rap activation is critical for MTOC polarization towards anti-Ig-coated beads and towards APCs. Activated Rap increases actin dynamics and promotes cytoskeletal reorganization by activating the actin-severing protein cofilin. We found that both disrupting the actin cytoskeleton with latrunculin A and blocking cofilin function prevented MTOC polarization, suggesting that Rap controls MTOC reorientation via its effects on actin dynamics. To assess how actin dynamics regulates the microtubule (MT) network, we tested the role of the actin-MT crosslinking protein IQGAP1 in BCR-induced MTOC polarization. We found that both Rap and cofilin controlled the accumulation of IQGAP1 at the site of Ag contact, and that depleting IQGAP1 prevented MTOC polarization. Thus Rap regulates the polarity of the MT network via its effects on the actin cytoskeleton and this may involve proteins such as IQGAP1 that link the actin and MT cytoskeletons.
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 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) | 0.003 | 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".