ATP-binding Cassette Transporter A1 Expression Disrupts Raft Membrane Microdomains through Its ATPase-related Functions
Bibliographic record
Abstract
ATP-binding cassette transporter A1 (ABCA1) is known to mediate cholesterol efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to influence functions of the plasma membrane, such as endocytosis and phagocytosis. Here, we report that ABCA1 expression results in a significant redistribution of cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae marker also redistributes from punctate caveolae-like structures to the general area of the plasma membrane upon ABCA1 expression. Furthermore, we observed significant reduction of Akt activation in ABCA1-expressing cells, consistent with raft disruption. Cholesterol content in the plasma membrane is, however, not altered. Moreover, we provide evidence that a non-functional ABCA1 with mutation in an ATP-binding domain, A937V, fails to redistribute cholesterol, sphingomyelin, or caveolin. A937V also fails to influence Akt activation. Finally, we show that apolipoprotein A-I preferentially associates with non-raft membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1 causes a change in overall lipid packing of the plasma membrane, likely through its ATPase-related functions. Such reorganization by ABCA1 effectively expands the non-raft membrane fractions and, consequentially, pre-conditions cells for cholesterol efflux.
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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 | 0.001 |
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".