WNT2 Regulates Gap Junction Function Through Beta-Catenin Dependent Adherens Junctions in Mouse Granulosa Cells.
Bibliographic record
Abstract
WNTs are secreted extracellular signaling molecules that exert their effects by binding to G protein-coupled receptors of the frizzled (FZD) family. WNT signaling has been found to influence cell proliferation, differentiation, survival, apoptosis, polarity, and migration. In granulosa cells, our recent evidence indicates that WNT2 signals through the FZD9 receptor to increase proliferation. In other cells, WNT signaling has been shown to regulate expression of the gap junction protein, connexin43 (Cx43). Previous work from our laboratories had demonstrated that Cx43 plays important roles in follicle development; hence the objective of this study was to determine if WNT2 signaling regulates Cx43 expression and/or gap junction function in mouse granulosa cells. In confocal immunolocalization experiments, we found that WNT2 is co-expressed with Cx43 in granulosa cells both in vivo and in culture. Gap junction function was assessed by quantifying intercellular coupling using dye injection and patch-clamp electrophysiology. Knockdown of WNT2 expression using transfected siRNA markedly reduced Cx43 expression and blocked gap junction function. Interestingly, WNT2 overexpression using a recombinant viral vector also reduced coupling between the cells. The total expression of Cx43 was slightly reduced as measured by western blot, but the amount in membrane plaques was severely reduced. β-catenin, a component of adherens junctions that can also enter the nucleus and regulate transcription, is the key component in canonical WNT signaling. When β-catenin expression was knocked down using siRNA, Cx43 expression and the number of Cx43-containing membrane plaques were reduced, as was gap junction function. Research by others has demonstrated that adherens junctions are essential for gap junction formation between cells. Using immunostaining, we found that β-catenin was mainly localized in the membranes between the granulosa cells but disappeared from this location after knockdown of WNT2 or β-catenin. WNT2 overexpression also reduced the amount of β-catenin in adherens junctions by causing its translocation from the membrane into the nucleus. In summary, our results indicate that the WNT2/β-catenin pathway regulates Cx43 expression and gap junction function in granulosa cells by modulating the extent of adherens junctions. This work was supported by grants to DB and GMK from the Canadian Institutes of Health Research. (platform)
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How this classification was reachedexpand
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 | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".