The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling
Why this work is in the frame
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Bibliographic record
Abstract
Fibroblast growth factor (FGF) signalling plays an essential role in early vertebrate development. However, the response to FGF requires endocytosis of the activated FGF receptor (FGFR) that is in part dependent on remodelling of the actin cytoskeleton. Recently we showed that the extended synaptotagmin family plasma membrane protein, E-Syt2, is an essential endocytic adapter for FGFR1. Here we show E-Syt2 is also an interaction partner for the p21-GTPase Activated Kinase PAK1. The phospholipid binding C2C domain of E-Syt2 specifically binds a site adjacent to the CRIB/GBD of PAK1. PAK1 and E-Syt2 selectively complex with FGFR1 and functionally cooperate in the FGF signalling. E-Syt2 binding suppresses actin polymerization and inhibits the activation of PAK1 by the GTPases Cdc42 and Rac. Interestingly, the E-Syt2 binding site on PAK1 extensively overlaps a site recently suggested to bind phospholipids. Our data suggest that PAK1 interacts with phospholipid membrane domains via E-Syt2, where it may cooperate in the E-Syt2-dependent endocytosis of activated FGFR1 by modulating cortical actin stability.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 it