Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes.
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. Diffe...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797093393820549120 |
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| author | Benz, P Blume, C Moebius, J Oschatz, C Schuh, K Sickmann, A Walter, U Feller, S Renné, T |
| author_facet | Benz, P Blume, C Moebius, J Oschatz, C Schuh, K Sickmann, A Walter, U Feller, S Renné, T |
| author_sort | Benz, P |
| collection | OXFORD |
| description | 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 alphaII-spectrin as such a VASP-interacting protein. alphaII-Spectrin binds to the VASP triple GP(5)-motif via its SH3 domain. cAMP-dependent protein kinase-mediated VASP phosphorylation at Ser157 inhibits alphaII-spectrin-VASP binding. VASP is dephosphorylated upon formation of cell-cell contacts and in confluent, but not in sparse cells, alphaII-spectrin colocalizes with nonphosphorylated VASP at cell-cell junctions. Ectopic expression of the alphaII-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 alphaII-spectrin binding-deficient VASP mutants fail to restore elevated permeability. We propose that alphaII-spectrin-VASP complexes regulate cortical actin cytoskeleton assembly with implications for vascular permeability. |
| first_indexed | 2024-03-07T03:59:43Z |
| format | Journal article |
| id | oxford-uuid:c4206914-426d-4bf3-9957-47f722da6b21 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:59:43Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:c4206914-426d-4bf3-9957-47f722da6b212022-03-27T06:21:18ZCytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4206914-426d-4bf3-9957-47f722da6b21EnglishSymplectic Elements at Oxford2008Benz, PBlume, CMoebius, JOschatz, CSchuh, KSickmann, AWalter, UFeller, SRenné, TDirected 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 alphaII-spectrin as such a VASP-interacting protein. alphaII-Spectrin binds to the VASP triple GP(5)-motif via its SH3 domain. cAMP-dependent protein kinase-mediated VASP phosphorylation at Ser157 inhibits alphaII-spectrin-VASP binding. VASP is dephosphorylated upon formation of cell-cell contacts and in confluent, but not in sparse cells, alphaII-spectrin colocalizes with nonphosphorylated VASP at cell-cell junctions. Ectopic expression of the alphaII-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 alphaII-spectrin binding-deficient VASP mutants fail to restore elevated permeability. We propose that alphaII-spectrin-VASP complexes regulate cortical actin cytoskeleton assembly with implications for vascular permeability. |
| spellingShingle | Benz, P Blume, C Moebius, J Oschatz, C Schuh, K Sickmann, A Walter, U Feller, S Renné, T Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title | Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title_full | Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title_fullStr | Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title_full_unstemmed | Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title_short | Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. |
| title_sort | cytoskeleton assembly at endothelial cell cell contacts is regulated by alphaii spectrin vasp complexes |
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