GIT2 Maintains Podocyte Architecture through Suppressing Rac1 Activity and Focal Adhesion Turnover
Bibliographic record
Abstract
Background: Podocyte foot processes are supported by the actin cytoskeleton which is precisely organized by Rho GTPases including Rac1. Overactivation of Rac1 in podocytes causes structural changes in foot processes and proteinuria. To elucidate the regulatory mechanism of Rac1, we performed proximity-based ligation assay and identified GIT2 as a Rac1-interacting protein in immortalized human podocytes (HP). Methods: Subcellular localization of endogenous GIT2 in HP was examined by immunocytochemistry. HP with GIT2 knockdown (KD), GIT2 overexpression (OE) and control (CTRL) cells were established using lentiviral transduction. Rac1 activity was assessed by pull-down assay. Cell areas were quantified in fixed cells stained by phalloidin. Focal adhesion dynamics were analyzed using time-lapse fluorescence microscopy in cells transfected with mRFP-paxillin. Subcellular localization of the tyrosine phosphatase, PTP1B, was monitored using time-lapse fluorescence microscopy. Results: GIT2 localized with paxillin in focal adhesions. GTP-bound (active) Rac1 levels were significantly higher in GIT2 KD HP than in CTRL. GIT2 KD elicited cell spreading with marked lamellipodial protrusions, which was significantly attenuated by the Rac1 inhibitor NSC23766. GIT2 KD HP had smaller focal adhesions than CTRL. Focal adhesion disassembly rate was significantly higher in GIT2 KD HP, resulting in shorter focal adhesion lifetime. Among the major focal adhesion proteins, tyrosine phosphorylation of p130Cas protein was most prominently increased in GIT2 KD HP, as compared with CTRL. PTP1B localization to focal adhesions was impaired in GIT2 KD HP. The phenotypes observed in GIT2 KD HP shown above were reversed by GIT2 OE. Conclusion: We demonstrated that GIT2 suppresses Rac1 activity in focal adhesions and contributes to maintaining podocyte morphology and function. Furthermore, we showed that GIT2 facilitates translocation of the PTP1B to focal adhesions where it dephosphorylates p130Cas, thereby suppressing local Rac1 activity.
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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 | 0.000 |
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".