Rab5 is a signalling GTPase involved in actin remodelling by receptor tyrosine kinases
| Autor: | Pier Paolo Di Fiore, Liliana B. Areces, Giorgio Scita, Letizia Lanzetti, Andrea Palamidessi |
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| Rok vydání: | 2004 |
| Předmět: |
Oncogene Proteins
Fusion Arp2/3 complex macromolecular substances environment and public health Receptor tyrosine kinase Mice Phosphatidylinositol 3-Kinases Animals Humans Actinin Small GTPase GTPase Cells Cultured Cytoskeleton Adaptor Proteins Signal Transducing rab5 GTP-Binding Proteins Platelet-Derived Growth Factor Multidisciplinary biology actin remodelling Kinase GTPase-Activating Proteins fungi Receptor Protein-Tyrosine Kinases Actin remodeling Fibroblasts Actin cytoskeleton Actins rac GTP-Binding Proteins Cell biology enzymes and coenzymes (carbohydrates) Mutation signal transduction ras Proteins biology.protein MDia1 biological phenomena cell phenomena and immunity Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Nature. 429:309-314 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature02542 |
| Popis: | Rab5 is a small GTPase involved in the control of intracellular trafficking, both at the level of receptor endocytosis and endosomal dynamics1. The finding that Rab5 can be activated by receptor tyrosine kinases (RTK)2 raised the question of whether it also participates in effector pathways emanating from these receptors. Here we show that Rab5 is indispensable for a form of RTK-induced actin remodelling, called circular ruffling. Three independent signals, originating from Rab5, phosphatidylinositol-3-OH kinase and Rac, respectively, are simultaneously required for the induction of circular ruffles. Rab5 signals to the actin cytoskeleton through RN-tre, a previously identified Rab5-specific GTPase-activating protein (GAP)3. Here we demonstrate that RN-tre has the dual function of Rab5-GAP and Rab5 effector. We also show that RN-tre is critical for macropinocytosis, a process previously connected to the formation of circular ruffles4,5. Finally, RN-tre interacts with both F-actin and actinin-4, an F-actin bundling protein. We propose that RN-tre establishes a three-pronged connection with Rab5, F-actin and actinin-4. This may aid crosslinking of actin fibres into actin networks at the plasma membrane. Thus, we have shown that Rab5 is a signalling GTPase and have elucidated the major molecular elements of its downstream pathway. |
| Databáze: | OpenAIRE |
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