A novel association between platelet filamin A and soluble N-ethylmaleimide sensitive factor attachment proteins regulates granule secretion

Background and ObjectiveThe molecular mechanisms that underpin platelet granule secretion remain poorly defined. Filamin A (FLNA) is an actin-crosslinking signaling scaffold protein whose role in exocytosis has not been explored despite evidence FLNA gene mutations confer defects humans.Methods ResultsUsing platelets from platelet-specific conditional Flna-knockout mice, we showed the loss of confers a severe defect alpha (α)- dense (δ)-granule exocytosis, as measured based on release factor 4 (aka CXCL4) adenosine triphosphate (ATP), respectively. This was observed following activation both immunoreceptor tyrosine-based motif (ITAM) by collagen-related peptide (CRP) G protein–coupled receptor (GPCR) thrombin thromboxane mimetic U46619. CRP–induced spikes intracellular calcium [Ca2+]i were impaired FLNA-null relative to controls, confirming regulates ITAM-driven proximal signaling. In contrast, GPCR-mediated response U46619 unaffected FLNA. Normal requires complexing soluble N-ethylmaleimide-sensitive attachment (SNARE) proteins synaptosomal-associated 23 (SNAP23) syntaxin-11 (STX11). We determined coimmunoprecipitates with SNAP23 STX11 upon stimulation.ConclusionFLNA GPCR-driven associates activation-dependent manner.