The F-BAR Protein PACSIN2 Regulates Platelet Intracellular Membrane Architecture and in Vivo Hemostatic Functions
Bibliographic record
Abstract
Abstract Proteins of the Bin-amphiphysin-Rvs (BAR) and Fes-CIP4 homology BAR (F-BAR) families bind and deform membranes, promoting in cells tubular invaginations reminiscent of the platelet open canalicular system (OCS) and megakaryocyte (MK) demarcation membrane system (DMS). Here we investigated the role of the F-BAR protein PACSIN2 in platelets and MKs. Spinning disk laser fluorescence confocal microscopy showed that PACSIN2 co-localized with the von Willebrand factor receptor subunit GPIbα at the openings of the OCS in platelets. Endogenous and over-expressed PACSIN2 associated with anastomosing tubular structures reminiscent of the pre-DMS in mouse bone marrow MKs. Pacsin2-null mice had mild thrombocytopenia and polycythemia, MK hyperplasia and splenomegaly. Pacsin2-null mice had a bleeding disorder, as evidenced by significantly prolonged tail bleeding and delayed in vivo thrombus formation following FeCl3 vascular injury, which was normalized by injection of WT platelets. However, Pacsin2-null platelets expressed P-selectin and activated the integrin αIIbβ3 normally in response to stimulation with thrombin and the GPVI-specific collagen-related peptide. In contrast, Pacsin2-null platelets had abnormal flattened morphology, with more and narrower OCS channels on their surface, compared to WT platelets. Together, the data indicate that the F-BAR protein PACSIN2 orchestrates the intracellular membrane architecture of platelets, thereby regulating their in vivo hemostatic functions. Disclosures No relevant conflicts of interest to declare.
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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".