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Recombinant scinderin, an F-actin severing protein, increases calcium-
induced release of serotonin from permeabilized platelets, an effect
blocked by two scinderin-derived actin-binding peptides and
phosphatidylinositol 4,5-bisphosphate
MG Marcu, L Zhang, K Nau-Staudt and JM Trifaro
Department of Pharmacology, Faculty of Medicine, University of Ottawa,
Ontario, Canada.
In response to vessel injury or exposure to different substances, platelets
undergo activation which consists of shape changes, formation of cellular
pseudopodia, aggregation, and secretion. These dramatic changes are
accompanied by cycles of actin depolymerization and polymerization.
Previous work has shown the presence in platelets of gelsolin and
scinderin, two Ca(2+)-dependent F-actin severing proteins. Recent published
evidence suggests that scinderin is a component of the exocytotic machinery
in chromaffin cells. The present work describes the preparation of
recombinant scinderin and peptides Sc-ABP1 and Sc- ABP2 with sequences
corresponding to two actin-binding sites of scinderin. Recombinant
scinderin and peptides Sc-ABP1 and Sc-ABP2 were tested for their effects on
Ca(2+)-induced serotonin release from digitonin permeabilized platelets.
The results indicated that recombinant scinderin potentiates Ca(2+)-evoked
serotonin release, an effect blocked in the presence of Sc-ABP1, Sc-ABP2,
exogenous gamma- actin, or the addition of phosphatidylinositol
4,5-bisphosphate (PIP2). In the presence of a mismatched peptide (MMP) the
potentiating effect of recombinant scinderin was not affected. Moreover,
Sc-ABP1, Sc-ABP2, and gamma-actin inhibited Ca(2+)-induced release of
serotonin in the absence of recombinant scinderin, suggesting an inhibition
of platelet endogenous scinderin. MMP was ineffective under these
conditions. The results suggest that F-actin disassembly, perhaps at a
specific site, is required for platelet secretion and that scinderin might
be an important component of the exocytotic machinery in platelets.
Volume 87,
Issue 1,
pp. 20-24,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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