Cited 0 times in Scipus Cited Count

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

Other Title
혈관내피세포에서 알파시누클레인 (alpha-Synuclein)에 의한 Weibel-Palade Body의 exocytosis 조절
김, 광수
대학원 의생명과학과
Doctor (2011)
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.

Appears in Collections:
Theses > Graduate School of Biomedical Sciences > Doctor
Ajou Authors
김, 광수
Full Text Link
Files in This Item:
There are no files associated with this item.


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.