RECOMBINANT SCINDERIN, AN F-ACTIN SEVERING PROTEIN, INCREASES CALCIUM-INDUCED RELEASE OF SEROTONIN FROM PERMEABILIZED PLATELETS, AN EFFECT BLOCKED BY 2 SCINDERIN-DERIVED ACTIN-BINDING PEPTIDES AND PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
Mg. Marcu et al., RECOMBINANT SCINDERIN, AN F-ACTIN SEVERING PROTEIN, INCREASES CALCIUM-INDUCED RELEASE OF SEROTONIN FROM PERMEABILIZED PLATELETS, AN EFFECT BLOCKED BY 2 SCINDERIN-DERIVED ACTIN-BINDING PEPTIDES AND PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE, Blood, 87(1), 1996, pp. 20-24
In response to vessel injury or exposure to different substances, plat
elets undergo activation which consists of shape changes, formation of
cellular pseudopodia, aggregation, and secretion, These dramatic chan
ges are accompanied by cycles of actin depolymerization and polymeriza
tion. Previous work has shown the presence in platelets of gelsolin an
d scinderin, two Ca2+-dependent F-actin severing proteins, Recent publ
ished evidence suggests that scinderin is a component of the exocytoti
c machinery in chromaffin cells. The present work describes the prepar
ation of recombinant scinderin and peptides Sc-ABP(1) and Sc-ABP(2) wi
th sequences corresponding to two actin-binding sites of scinderin, Re
combinant scinderin and peptides Sc-ABP(1) and So ABP, were tested for
their effects on Ca2+-induced serotonin release from digitonin permea
bilized platelets, The results indicated that recombinant scinderin po
tentiates Ca2+-evoked serotonin release, an effect blocked in the pres
ence of Sc-ABP(1), Sc-ABP(2), exogenous gamma-actin, or the addition o
f phosphatidylinositol 4,5-bisphosphate (PIP2). In the presence of a m
ismatched peptide (MMP) the potentiating effect of recombinant scinder
in was not affected, Moreover, Sc-ABP(1), Sc-ABP(2), and gamma-actin i
nhibited Ca2+-induced release of serotonin in the absence of recombina
nt scinderin, suggesting an inhibition of platelet endogenous scinderi
n, MMP was ineffective under these conditions. The results suggest tha
t F-actin disassembly, perhaps at a specific site, is required for pla
telet secretion and that scinderin might be an important component of
the exocytotic machinery in platelets. (C) 1996 by The American Societ
y of Hematology.