The RapGEF PDZ-GEF2 is required for maturation of cell–cell junctions
| Autor: | Judith Klumperman, Nadia Dubé, Johannes L. Bos, Marjolein J. Vliem, Willem-Jan Pannekoek, Viola Oorschot, Holger Rehmann, Matthijs R.H. Kooistra |
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| Rok vydání: | 2008 |
| Předmět: |
Chemistry
Activator (genetics) Cadherin PDZ domain Regulator rap1 GTP-Binding Proteins Epithelial Cells Adherens Junctions Cell Biology Cadherins Cell junction Cell biology Adherens junction rap GTP-Binding Proteins Cell Adhesion Guanine Nucleotide Exchange Factors Humans Rap1 Endothelium Vascular Guanine nucleotide exchange factor |
| Zdroj: | Cellular Signalling. 20:1608-1615 |
| ISSN: | 0898-6568 |
| Popis: | The small G-protein Rap1 is a critical regulator of cell–cell contacts and is activated by the remodeling of adherens junctions. Here we identify the Rap1 guanine nucleotide exchange factor PDZ-GEF2 as an upstream activator of Rap1 required for the maturation of adherens junctions in the lung carcinoma cells A549. Knockdown of PDZ-GEF2 results in the persistence of adhesion zippers at cell–cell contacts. Activation of Rap1A rescues junction maturation in absence of PDZ-GEF2, demonstrating that Rap1A is downstream of PDZ-GEF2 in this process. Moreover, depletion of Rap1A, but not Rap1B, impairs adherens junction maturation. siRNA for PDZ-GEF2 also lowers the levels of E-cadherin, an effect that can be mimicked by Rap1B, but not Rap1A siRNA. Since junctions in Rap1B depleted cells have a mature appearance, these data suggest that PDZ-GEF2 activates Rap1A and Rap1B to perform different functions. Our results present the first direct evidence that PDZ-GEF2 plays a critical role in the maturation of adherens junctions. |
| Databáze: | OpenAIRE |
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