The F-BAR Protein PACSIN 2 Specifically Coats the Anastomosing Intracellular Membrane Systems of Platelets and Megakaryocytes,
Bibliographic record
Abstract
Abstract Abstract 3261 Megakaryocyte (MK) maturation and platelet formation are associated with extensive intracellular membrane rearrangements. However, the cellular proteins and mechanisms responsible for the formation of the platelet open canalicular system (OCS) are unknown. PACSIN 1–3 belong to the novel family of F-BAR domain-containing proteins, which bind and deform membranes, promoting tubular invaginations. Blood platelets and MKs contain the ubiquitously expressed PACSIN 2, but not PACSIN 1 or 3, as evidenced by intracellular flow cytometry and immunoblot analysis. Spinning disk laser fluorescence confocal microscopy revealed a specific association between PACSIN 2 and tubular structures in human platelets. PACSIN 2 did not colocalize with granule or lysosome markers, i.e. CD62P, CD63 and LAMP1, suggesting that it coats the OCS. In mouse MKs, PACSIN 2 was distributed through the cell body and colocalized with the membrane marker, CD61. Immunoprecipitation of PACSIN 2 from human platelet lysates pulled down filamin A (FlnA), a major platelet cytoskeletal protein. The interaction required PACSIN 2 F-BAR domain, as evidenced by in vitro binding assays using recombinant proteins. Mice lacking FlnA in the MK lineage have a severe thrombocytopenia with large platelets (Falet et al, J Exp Med 2010; Jurak Begonja et al, Blood 2011). In contrast to wild type platelets, FlnA-null platelets had diffuse PACSIN 2 staining and abnormal intracellular membrane structures, suggesting that the PACSIN 2-FlnA interaction is necessary for the integrity of the platelet intracellular membrane systems. PACSIN 2-null mice had a mild thrombocytopenia, enlarged spleens and increased spleen megakaryopoiesis. Together, the data shows that PACSIN 2 is expressed in platelets and MKs, where it specifically coats the anastomosing intracellular membrane systems in cooperation with FlnA. 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) | 0.002 | 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".