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First published online December 20, 2006
doi: 10.1242/10.1242/jcs.03306


Journal of Cell Science 120, 17-22 (2007)
Published by The Company of Biologists 2007
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Rap1: a key regulator in cell-cell junction formation

Matthijs R. H. Kooistra, Nadia Dubé and Johannes L. Bos*

Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands


Figure 1
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Fig. 1. Overview of the Rap1 signalling network. Adapted from Bos, 2005 with permission (Bos, 2005Go). DAG, diacylglycerol; E/V, Ena/Vasp; GPCR, G-protein coupled receptor; PIP3, phosphoinositol-tri-phosphate; PLC, phospholipase C; RTK, receptor tyrosine kinase.

 

Figure 2
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Fig. 2. Schematic overview of adherens junctions and tight junctions. {alpha}, {alpha}-catenin; AF6, afadin/AF6; AJ, adherens junctions; ß, ß-catenin; JAMs, junctional adhesion molecules; p120, p120catenin; TJ, tight junctions; ZO, zona occludens.

 

Figure 3
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Fig. 3. Activation of Rap1 in endothelial cells induces cell-cell junction maturation. Anti-VE-cadherin and F-actin staining of HUVE cells treated for 30 minutes with vehicle or the Epac-specific cAMP analog 007. Stimulation with 007 clearly increased cell-cell junction maturation: the adherens junctions form a smoother line between the cells. Endothelial cell permeability is reduced as a biological consequence of the junction tightening (Bar, 10 µm).

 

Figure 4
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Fig. 4. Model for the involvement of Rap1 in cell-cell junction formation. At initial cell-cell contacts, C3G bound to E-cadherin is activated, resulting in Rap1 activation. Upon maturation, C3G is displaced by ß-catenin, which interacts with PDZ-GEF to further activate Rap1. Also, extracellular stimuli, including those that stimulate production of cAMP which activates Epac, induce Rap1 activation.

 





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