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. 2014 Dec 3;8:392. doi: 10.3389/fnins.2014.00392

Figure 3.

Figure 3

VE-cadherin and CCM1 act in concert to establish endothelial polarization and lumen formation. Rap1 regulates the junctional localization of CCM1 and mediates CCM1 activity in endothelial polarization and lumen formation. CCM1 stabilizes VE-cadherin at AJs, by associating with ß-catenin and inhibiting dissociation of ß-catenin from AJs. Thereby, nuclear accumulation of ß-catenin and ß-catenin transcriptional signaling is impaired. VE-cadherin promotes the apical localization and activation of the Par3 polarity complex. While VE-cadherin is needed for phosphorylation of PKCξ, CCM1/Rap1 is responsible for the junctional recruitment of the polarity complex. The accumulation of podocalyxin (PODXL) at the presumptive apical membrane is controlled by VE-cadherin and ß1 integrin. PODXL in turn recruits moesin and filamentous actin (F-actin) to the apical domain initiating endothelial lumen formation.