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Regulation of Weibel-Palade body exocytosis by alpha-synuclein in endothelial cells.
DC Field | Value | Language |
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dc.contributor.author | Kim, KS | - |
dc.contributor.author | Park, JY | - |
dc.contributor.author | Jou, I | - |
dc.contributor.author | Park, SM | - |
dc.date.accessioned | 2011-04-28T04:47:16Z | - |
dc.date.available | 2011-04-28T04:47:16Z | - |
dc.date.issued | 2010 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/2491 | - |
dc.description.abstract | alpha-Synuclein is a small presynaptic protein implicated in the pathogenesis of Parkinson disease. Nevertheless, its physiological roles and mechanisms remain incompletely understood. alpha-Synuclein is not only expressed in neurons but also in the vascular endothelium, which contains intracellular granules called Weibel-Palade bodies (WPBs) that contain a number of chemokines, adhesive molecules, and inflammatory cytokines. This study explored whether the exocytosis of WPB is regulated by alpha-synuclein. Phorbol 12-myristate 13-acetate-, thrombin-, or forskolin-induced von Willebrand factor release or translocation of P-selectin from endothelial cells were inhibited by alpha- and beta-synuclein but not gamma-synuclein. Three point mutants (A30P, A53T, and E46K) found in familial Parkinson disease also inhibited WPB exocytosis similar to that of wild-type alpha-synuclein. Furthermore, the negative regulation of WPB exocytosis required the N terminus or the nonamyloid beta-component of Alzheimer disease amyloid region of alpha-synuclein, but not the C-terminal acidic tail, and alpha-synuclein affected WPB exocytosis through interference with RalA activation by enhancing the interaction of RalGDS-beta-arrestin complexes. Immuno-EM analysis revealed that alpha-synuclein was localized close to WPBs. These findings imply that alpha-synuclein plays as a negative regulator in WPB exocytosis in endothelial cells. | - |
dc.language.iso | en | - |
dc.subject.MESH | Alzheimer Disease | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Endothelial Cells | - |
dc.subject.MESH | Endothelium, Vascular | - |
dc.subject.MESH | Exocytosis | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Microscopy, Confocal | - |
dc.subject.MESH | Microscopy, Immunoelectron | - |
dc.subject.MESH | Models, Biological | - |
dc.subject.MESH | Parkinson Disease | - |
dc.subject.MESH | Point Mutation | - |
dc.subject.MESH | Protein Transportv | - |
dc.subject.MESH | Weibel-Palade Bodies | - |
dc.subject.MESH | alpha-Synuclein | - |
dc.subject.MESH | ral GTP-Binding Proteins | - |
dc.title | Regulation of Weibel-Palade body exocytosis by alpha-synuclein in endothelial cells. | - |
dc.type | Article | - |
dc.identifier.pmid | 20448034 | - |
dc.identifier.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898423/ | - |
dc.contributor.affiliatedAuthor | 주, 일로 | - |
dc.contributor.affiliatedAuthor | 박, 상면 | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.1074/jbc.M110.103499 | - |
dc.citation.title | The Journal of biological chemistry | - |
dc.citation.volume | 285 | - |
dc.citation.number | 28 | - |
dc.citation.date | 2010 | - |
dc.citation.startPage | 21416 | - |
dc.citation.endPage | 21425 | - |
dc.identifier.bibliographicCitation | The Journal of biological chemistry, 285(28). : 21416-21425, 2010 | - |
dc.identifier.eissn | 1083-351X | - |
dc.relation.journalid | J000219258 | - |
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