Insulin-induced actin remodelling and the localization of signalling molecules
Bibliographic record
Abstract
Insulin promotes the translocation of glucose transporter isoform 4 (GLUT4) from intracellular pools to the surface of muscle and fat cells via a mechanism dependent on phosphatidylinositol 3-kinase (PI3-kinase), actin cytoskeletal remodelling and the v-SNARE, VAMP2. In cells expressing receptors for the growth factor PDGF, this ligand also robustly activates PI3-kinase and induces actin remodelling, raising the question of whether it utilizes similar mechanisms to insulin in mobilizing GLUT4. In L6 myoblasts stably expressing myc-tagged GLUT4, we show that both insulin and PDGF promote GLUT4 exocytosis and glucose uptake albeit with different time courses. Interestingly, we show that insulin but not PDGF rely on the actin cytoskeleton and tetanus toxin light chain-sensitive v-SNARES for GLUT4myc translocation to the cell surface. These results suggest that insulin and PDGF rely differentially on the actin cytoskeleton and on tetanus toxin sensitive v-SNARES for the increase in surface GLUT4. In order to understand the functional role of the actin cytoskeleton in L6 cells, we tested the hypothesis that actin filament remodelling determines the location of insulin signalling molecules. We show that insulin treatment leads to a rapid rearrangement of actin filaments into submembrane structures where specific key insulin signalling molecules colocalized with the actin structures. We propose that insulin-stimulated actin remodelling may spatially coordinate the localized generation of PI-3,4,5-P3 and recruitment of Akt, ultimately leading to GLUT4 insertion at the plasma membrane. Actin remodelling is a tightly regulated process and involves a wide variety of actin binding proteins. Among such families of proteins are the Actin-Depolymerizing Factor (ADF)/Cofilins, which have been shown to be essential for regulating actin turnover in other cellular systems. We show here that insulin promotes the dephosphorylation of cofilin1 in a time- and P13-kinase-dependent manner. Moreover, insulin enhanced the colocalization of cofilin1 with the mesh-like actin structures. Knockdown of cofilin1 expression by siRNA-mediated gene silencing altered actin dynamics and inhibited GLUT4 translocation to the cell surface in insulin-stimulated cells. These results suggest that insulin regulates the activity of cofilin1 in order to promote actin remodelling and to facilitate GLUT4 translocation and fusion with the plasma membrane.
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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".