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Guanine exchange factor RalGDS mediates exocytosis of Weibel-Palade bodies from endothelial cells
| Content Provider | Scilit |
|---|---|
| Author | Rondaij, Mariska G. Bierings, Ruben van Agtmaal, Ellen L. Gijzen, Karina A. Sellink, Erica Kragt, Astrid Ferguson, Stephen S. G. Mertens, Koen Hannah, Matthew J. van Mourik, Jan A. Fernandez-Borja, Mar Voorberg, Jan |
| Copyright Year | 2008 |
| Description | The small GTP-binding protein Ral has been implicated in regulated exocytosis via its interaction with the mammalian exocyst complex. We have previously demonstrated that Ral is involved in exocytosis of Weibel-Palade bodies (WPBs). Little is known about intracellular signaling pathways that promote activation of Ral in response to ligand binding of G protein–coupled receptors. Here we show that RNAi-mediated knockdown of RalGDS, an exchange factor for Ral, results in inhibition of thrombin- and epinephrine-induced exocytosis of WPBs, while overexpression of RalGDS promotes exocytosis of WPBs. A RalGDS variant lacking its exchange domain behaves in a dominant negative manner by blocking release of WPBs. We also provide evidence that RalGDS binds calmodulin (CaM) via an amino-terminal CaM-binding domain. RalGDS association to CaM is required for Ral activation because a cell-permeable peptide comprising this RalGDS CaM-binding domain inhibits Ral activation and WPB exocytosis. Together our findings suggest that RalGDS plays a vital role in the regulation of Ral-dependent WPB exocytosis after stimulation with Ca2+- or cAMP-raising agonists. |
| Related Links | http://www.bloodjournal.org/content/112/1/56.full.pdf |
| Ending Page | 63 |
| Page Count | 8 |
| Starting Page | 56 |
| DOI | 10.1182/blood-2007-07-099309 |
| Journal | Blood |
| Issue Number | 1 |
| Volume Number | 112 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2008-07-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Ralgds Protein Rnai Binding Wpb Exocytosis Cam Wpbs Ral Activation Journal: Blood (Vol- 19, Issue- 1) |
| Content Type | Text |
| Resource Type | Article |
