|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 October 2002, Vol. 100, No. 7, pp. 2506-2514
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Evidence that  -synuclein functions as a negative regulator of
Ca++-dependent -granule release from human
platelets
Sang Myun Park,
Han Young Jung,
Hyun Ok Kim,
Hyangshuk Rhim,
Seung R. Paik,
Kwang Chul Chung,
Jeon Han Park, and
Jongsun Kim
From the Department of Microbiology and Brain Korea
21 Project of Medical Sciences, Department of Clinical
Pathology, and Department of Pharmacology, Yonsei University College of
Medicine, Seoul, Korea; Research Institute of Molecular Genetics,
Catholic University College of Medicine, Seoul, Korea; and Department
of Biochemistry, Inha University College of Medicine, Inchon, Korea.
 -Synuclein has been implicated in the pathogenesis of Parkinson
disease (PD) and related neurodegenerative disorders. More recently, it
has been suggested to be an important regulatory component of vesicle
transport in neuronal cells. -Synuclein is also highly expressed in
platelets and is loosely associated with the membrane of the secretory
-granules. However, the functional significance of these
observations is unknown. In this study, the possible function of
-synuclein in vesicle transport, with particular regard to
-granule release from the platelets, was investigated. The results
showed that ionomycin- or thrombin-induced -granule secretion was
inhibited by exogenous -synuclein addition in a dose-dependent
manner. However, [3H]5-HT release from the dense granules
and hexosaminidase release from the lysosomal granules were not
affected. Two point mutants (A30P and A53T) found in some familial
types of PD, in addition to  -synuclein and -synuclein112,
effectively inhibited PF4 release from the -granules. However, the
deletion mutants, which completely lacked either the N-terminal region
or the C-terminal tail, did not affect -granule release.
Interestingly, exogenously added -synuclein appeared to enter the
platelets but did not change the Ca++ level in the
platelets at the resting state and the increase in the Ca++
level on stimulation. Electron microscopy also supported that -synuclein inhibits -granule release. These results suggest that
-synuclein may function as a specific negative regulator of
-granule release in platelets.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. L. Sousa, S. Bellani, M. Giannandrea, M. Yousuf, F. Valtorta, J. Meldolesi, and E. Chieregatti
{alpha}-Synuclein and Its A30P Mutant Affect Actin Cytoskeletal Structure and Dynamics
Mol. Biol. Cell,
August 15, 2009;
20(16):
3725 - 3739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ungerer, M. Peluso, A. Gillitzer, S. Massberg, U. Heinzmann, C. Schulz, G. Munch, and M. Gawaz
Generation of Functional Culture-Derived Platelets From CD34+ Progenitor Cells to Study Transgenes in the Platelet Environment
Circ. Res.,
September 3, 2004;
95(5):
e36 - e44.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
