VE-Cadherin Signaling Induces EB3 Phosphorylation to Suppress Microtubule Growth and Assemble Adherens Junctions
| Autor: | Alexander Garcia, Barry Kreutz, Asrar B. Malik, Luiza Idalino, Fei Huang, Melissa Geyer, Nazila Daneshjou, Yulia Komarova, Dolly Mehta |
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| Rok vydání: | 2012 |
| Předmět: |
Biology
Microtubules Time-Lapse Imaging Article Adherens junction Calmodulin Antigens CD Cell Adhesion Homeostasis Humans Calcium Signaling Phosphorylation Cell adhesion Molecular Biology Cells Cultured Calcium signaling Microscopy Confocal Phospholipase C Phospholipase C gamma Cadherin Calcineurin Endoplasmic reticulum Endothelial Cells Adherens Junctions Cell Biology Cadherins Cell biology Enzyme Activation Kinetics src-Family Kinases Calcium Endothelium Vascular VE-cadherin Microtubule-Associated Proteins Protein Processing Post-Translational Protein Binding |
| Zdroj: | Molecular Cell. 48:914-925 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2012.10.011 |
| Popis: | Summary Vascular endothelial (VE)-cadherin homophilic adhesion controls endothelial barrier permeability through assembly of adherens junctions (AJs). We observed that loss of VE-cadherin-mediated adhesion induced the activation of Src and phospholipase C (PLC)γ2, which mediated Ca 2+ release from endoplasmic reticulum (ER) stores, resulting in activation of calcineurin (CaN), a Ca 2+ -dependent phosphatase. Downregulation of CaN activity induced phosphorylation of serine 162 in end binding (EB) protein 3. This phospho-switch was required to destabilize the EB3 dimer, suppress microtubule (MT) growth, and assemble AJs. The phospho-defective S162A EB3 mutant, in contrast, induced MT growth in confluent endothelial monolayers and disassembled AJs. Thus, VE-cadherin outside-in signaling regulates cytosolic Ca 2+ homeostasis and EB3 phosphorylation, which are required for assembly of AJs. These results identify a pivotal function of VE-cadherin homophilic interaction in modulating endothelial barrier through the tuning of MT dynamics. |
| Databáze: | OpenAIRE |
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