Regulation of Weibel-Palade Body Exocytosis by alpha-Synuclein in Endothelial Cells

a-Synuclein (a-syn) is a small presynaptic protein implicated in the pathogenesis of Parkinson’s disease. Although gathering evidence has been proposed for its physiological roles, the precise roles of a-synuclein and mechanisms remain incompletely understood. a-Synuclein is not only expressed in neuron, but also in vascular endothelium. Endothelial cells contain 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 a-synuclein. Results showed that PMA-, thrombin- or forskolin-induced VWF release or translocation of P-selectin from Human Umbilical Vein Endothelial Cells (HUVECs) were inhibited by overexpression of a- and b-synuclein, but not g-synuclein. The overexpression of three point mutants (A30P, A53T and E46K) found in familial Parkinson’s disease inhibited WPB exocytosis similar to that of wild-type a-synuclein. Results also showed that the negative regulation of WPB exocytosis required the N-terminus or NAC region of a-synuclein, but not C-terminal acidic tail, and that a-synuclein affected WPB exocytosis through interference with RalA activation by enhancing the interaction of RalGDS/b-arrestin complexes. Immuno-EM analysis revealed that a-synuclein was localized close to WPB. These findings imply that a-synuclein plays as a negative regulator in WPB exocytosis in endothelial cells.

Author dc:creator

• 김, 광수

Contributors dc:contributor

• 주, 일로
• 박, 상면
• 대학원 의생명과학과
• 105432

• 혈관내피세포
• Weibel-Palade Body
• exocytosis
• Endothelial cells
• 알파시누클레인
• alpha-Synuclein

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000011658
000000011658

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/4381