Figure 6.

Proposed model for regulation of platelet granule secretion by filamin A (FLNA). FLNA regulates platelet granule secretion in an agonist-dependent manner. (A) Ligation of the platelet G protein–coupled receptors (GPCR) by thrombin (aka F2) activates phospholipase C beta (aka PLCB1), which converts phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Inositol 1,4,5-trisphosphate promotes the release of intracellular Ca²⁺ ([Ca²⁺]_i), and DAG activates protein kinase C epsilon (aka PRKCE). Both Ca²⁺ and DAG drive granule secretion. Notably, FLNA associates with SNAP23 and STX11 to participate in granule fusion with the plasma membrane thus mediating secretion. (B) Ligation of an immunoreceptor tyrosine-based activation motif-coupled (ITAM) receptor (GPVI, aka GP6) with collagen-related peptide (CRP) activates SYK via SRC family kinases (FYN and LYN). Loss of FLNA expression precludes the normal rise in [Ca²⁺]_i, thus blocking platelet secretion at the second messenger level upstream.