EphB1 interaction with caveolin-1 in endothelial cells modulates caveolae biogenesis
| Autor: | Radu V. Stan, Chinnaswamy Tiruppathi, Stephen M. Vogel, Gary C.H. Mo, Richard D. Minshall, Mark Henkemeyer, Asrar B. Malik, Peter T. Toth, Jalees Rehman, Sushil Chandra Regmi, Dong-Mei Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Receptor EphB1 Caveolin 1 Ephrin-B1 Caveolae Nitric Oxide Receptor tyrosine kinase Mice Animals Phosphorylation Molecular Biology biology Endothelial Cells Receptor Protein-Tyrosine Kinases Articles Cell Biology Ligand (biochemistry) Cell biology Mice Inbred C57BL Membrane Trafficking cardiovascular system biology.protein Female Biogenesis Intracellular Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Caveolae, the cave-like structures abundant in endothelial cells (ECs), are important for multiple signaling processes such as production of nitric oxide and caveolae-mediated intracellular trafficking. Using superresolution microscopy, fluorescence resonance energy transfer, and biochemical analysis, we observed that the EphB1 receptor tyrosine kinase constitutively interacts with caveolin-1 (Cav-1), the key structural protein of caveolae. Activation of EphB1 with its ligand Ephrin B1 induced EphB1 phosphorylation and the uncoupling EphB1 from Cav-1 and thereby promoted phosphorylation of Cav-1 by Src. Deletion of Cav-1 scaffold domain binding (CSD) motif in EphB1 prevented EphB1 binding to Cav-1 as well as Src-dependent Cav-1 phosphorylation, indicating the importance of CSD in the interaction. We also observed that Cav-1 protein expression and caveolae numbers were markedly reduced in ECs from EphB1-deficient (EphB1−/−) mice. The loss of EphB1 binding to Cav-1 promoted Cav-1 ubiquitination and degradation, and hence the loss of Cav-1 was responsible for reducing the caveolae numbers. These studies identify the crucial role of EphB1/Cav-1 interaction in the biogenesis of caveolae and in coordinating the signaling function of Cav-1 in ECs. |
| Databáze: | OpenAIRE |
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