Spatial Regulation of Cyclic AMP-Epac1 Signaling in Cell Adhesion by ERM Proteins
| Autor: | Matthijs R.H. Kooistra, Holger Rehmann, Fried J. T. Zwartkruis, Leo S. Price, Jun Zhao, Johannes L. Bos, Kees Jalink, Martijn Gloerich, Marjolein J. Vliem, Bas Ponsioen, Zhongchun Zhang, Laila Ritsma |
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| Rok vydání: | 2010 |
| Předmět: |
Small interfering RNA
Recombinant Fusion Proteins Small G Protein Biology Cell Line Receptors G-Protein-Coupled Cell membrane Radixin Two-Hybrid System Techniques Cell Adhesion Cyclic AMP medicine Animals Guanine Nucleotide Exchange Factors Humans Cell adhesion Molecular Biology Cell Membrane Microfilament Proteins Membrane Proteins rap1 GTP-Binding Proteins Articles Cell Biology Extracellular Matrix Cell biology Cytoskeletal Proteins medicine.anatomical_structure Membrane protein Guanine nucleotide exchange factor Signal transduction Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 30:5421-5431 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00463-10 |
| Popis: | Epac1 is a guanine nucleotide exchange factor for the small G protein Rap and is involved in membrane-localized processes such as integrin-mediated cell adhesion and cell-cell junction formation. Cyclic AMP (cAMP) directly activates Epac1 by release of autoinhibition and in addition induces its translocation to the plasma membrane. Here, we show an additional mechanism of Epac1 recruitment, mediated by activated ezrin-radixin-moesin (ERM) proteins. Epac1 directly binds with its N-terminal 49 amino acids to ERM proteins in their open conformation. Receptor-induced activation of ERM proteins results in increased binding of Epac1 and consequently the clustered localization of Epac1 at the plasma membrane. Deletion of the N terminus of Epac1, as well as disruption of the Epac1-ERM interaction by an interfering radixin mutant or small interfering RNA (siRNA)-mediated depletion of the ERM proteins, impairs Epac1-mediated cell adhesion. We conclude that ERM proteins are involved in the spatial regulation of Epac1 and cooperate with cAMP- and Rap-mediated signaling to regulate adhesion to the extracellular matrix. |
| Databáze: | OpenAIRE |
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