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- Title
Cytoskeleton assembly at endothelial cell--cell contacts is regulated by αII-spectrin--VASP complexes.
- Authors
Benz, Peter M.; Blume, Constanze; Moebius, Jan; Oschatz, Chris; Schuh, Kai; Sickmann, Albert; Walter, Ulrich; Feller, Stephan M.; Renné, Thomas
- Abstract
Directed cortical actin assembly is the driving force for intercellular adhesion. Regulated by phosphorylation, vasodilator-stimulated phosphoprotein (VASP) participates in actin fiber formation. We screened for endothelial proteins, which bind to VASP, dependent on its phosphorylation status. Differential proteomics identified αII-spectrin as such a VASP-interacting protein. αII-Spectrin binds to the VASP triple GP[sub 5]-motif via its SH3 domain, cAMP-dependent protein kinase-mediated VASP phosphorylation at Ser 157 inhibits αII-spectrin-VASP binding. VASP is dephosphorylated upon formation of cell-cell contacts and in confluent, but not in sparse cells, αII-spectrin colocalizes with nonphosphorylated VASP at cell-cell junctions. Ectopic expression of the αII-spectrin SH3 domain at cell-cell contacts translocates VASP, initiates cortical actin cytoskeleton formation, stabilizes cell--cell contacts, and decreases endothelial permeability. Conversely, the permeability of VASP-deficient endothelial cells (ECs) and microvessels of VASP-null mice increases. Reconstitution of VASP-deficient ECs rescues barrier function, whereas αII-spectrin binding-deficient VASP mutants fail to restore elevated permeability. We propose that αII-spectrin-VASP complexes regulate cortical actin cytoskeleton assembly with implications for vascular permeability.
- Subjects
CYTOSKELETON; CELL adhesion molecules; ENDOTHELIUM; CELL communication; VASODILATORS; PHOSPHOPROTEINS; ACTIN
- Publication
Journal of Cell Biology, 2008, Vol 180, Issue 1, p205
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200709181