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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1782-1788
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Molecular mechanisms of platelet exocytosis: role of SNAP-23
and syntaxin 2 and 4 in lysosome release
Dong Chen,
Paula P. Lemons,
Todd Schraw, and
Sidney W. Whiteheart
From the Department of Biochemistry, University of
Kentucky College of Medicine, Lexington, KY.
On stimulation by strong agonists, platelets release the contents
of 3 storage compartments in 2 apparent waves of exocytosis. The first
wave is the release of - and dense core granule contents and the
second is the release of lysosomal contents. Using a streptolysin O-permeabilized platelet exocytosis assay, we show that hexosaminidase release is stimulated by either Ca++ or by GTP- -S. This
release step retains the same temporal separation from serotonin
release as seen in intact platelets. This assay system was also used to
dissect the molecular mechanisms of lysosome exocytosis. Lysosome
release requires adenosine triphosphate and the general membrane fusion
protein, N-ethylmaleimide sensitive factor. Uniquely, 2 syntaxin
t-SNAREs, syntaxin 2 and 4, which localize to granules and
open canalicular membranes, together with the general target membrane
SNAP receptor (t-SNARE) protein SNAP-23 appear to make up the
heterodimeric t-SNAREs required for lysosome exocytosis.
These studies further show that regardless of stimuli (Ca++
or GTP- -S) serotonin and hexosaminidase release requires the same
membrane fusion machinery.

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