Evidence that α-synuclein functions as a negative regulator of Ca++-dependent α-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, Jongsun Kim

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41 Citations (Scopus)


α-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. α-Synuclein is also highly expressed in platelets and is loosely associated with the membrane of the secretory α-granules. However, the functional significance of these observations is unknown. In this study, the possible function of α-synuclein in vesicle transport, with particular regard to α-granule release from the platelets, was investigated. The resuits showed that ionomycin- or thrombin-induced α-granule secretion was inhibited by exogenous α-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 β-synuclein and α-synuclein112, effectively inhibited PF4 release from the α-granules. However, the deletion mutants, which completely lacked either the N-terminal region or the C-terminal tail, did not affect α-granule release. Interestingly, exogenously added α-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 α-synuclein inhibits α-granule release. These results suggest that α-synuclein may function as a specific negative regulator of α-granule release in platelets.

Original languageEnglish
Pages (from-to)2506-2514
Number of pages9
Issue number7
Publication statusPublished - 2002 Oct 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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