Abstract 316: Adap1 Prevents Cardiomyocyte Hypertrophy by Interfering with Integrin Signaling
Bibliographic record
Abstract
The Arf GTPase activating protein with dual PH domains 1 (Adap1), a putative regulator of the small G protein ADP-ribosylation factor 6 (Arf6), might be expressed to some extent in the heart. Although Arf6 roles in cardiomyocytes are not well defined, this small G protein was shown to alter surface expression of integrins in other cell types. Considering the importance of integrins on cellular mechanisms of adhesion and spreading, we hypothesized that Adap1 might impact cardiomyocyte hypertrophy by regulating integrin signaling . In order to determine the role of Adap1 in cardiomyocytes, we analyzed its cardiac expression in Sprague Dawley rats. Comparatively to its high mRNA expression in the brain, we showed that Adap1 transcript is expressed at relatively low levels in the heart of adult and neonatal rats. However, Western blot detection of Adap1 showed that it is well expressed in the whole heart of adult and neonatal rats at levels reaching 13% and 17% relative to the brain, respectively. Moreover, Adap1 was 3-fold more abundant in isolated rat neonatal ventricular cardiomyocyte (RNVC) comparatively to partially enriched non-cardiomyocyte cells. Adenoviral-mediated overexpression of ADAP1 partially prevented the increase in cell surface area of cultured RNVCs in response to increasing serum concentrations. Interestingly, ADAP1 overexpression completely blocked constitutively active mutant Mek1- and phenylephrine-induced hypertrophy of RNVCs. In these conditions, ADAP1 did not impair the Mek1ca-induced fetal gene program in RNVCs, suggesting that its anti-hypertrophic effect was not mediated by transcriptional regulation. In fact, cell surface biotin labeling indicated that ADAP1 significantly reduced the localization of integrin β1 at the membrane of RNVCs without changing its total expression. Strikingly, integrin β1 was almost completely absent from the surface of RNVCs overexpressing both ADAP1 and Mek1ca. These findings demonstrate for the first time that Adap1 expressed in cardiomyocytes interferes with the surface expression of integrin β1, thereby slowing the development of hypertrophy in vitro. Further in vivo studies are needed to characterize the anti-hypertrophic function of Adap1 in response to pathological stresses.
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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) | 0.003 | 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".