WNT2 Regulates Gap Junction Function Through Beta-Catenin Dependent Adherens Junctions in Mouse Granulosa Cells.
Notice bibliographique
Résumé
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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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».