TY - JOUR
T1 - Molecular mechanisms of platelet exocytosis
T2 - Role of SNAP-23 and syntaxin 2 and 4 in lysosome release
AU - Chen, Dong
AU - Lemons, Paula P.
AU - Schraw, Todd
AU - Whiteheart, Sidney W.
PY - 2000/9/1
Y1 - 2000/9/1
N2 - 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 α- 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-γ-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-γ-S) serotonin and hexosaminidase release requires the same membrane fusion machinery. (C) 2000 by The American Society of Hematology.
AB - 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 α- 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-γ-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-γ-S) serotonin and hexosaminidase release requires the same membrane fusion machinery. (C) 2000 by The American Society of Hematology.
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U2 - 10.1182/blood.v96.5.1782
DO - 10.1182/blood.v96.5.1782
M3 - Article
C2 - 10961877
AN - SCOPUS:0034283702
SN - 0006-4971
VL - 96
SP - 1782
EP - 1788
JO - Blood
JF - Blood
IS - 5
ER -