Monomeric structure of FLNa and partners in platelets. The amino-terminal ABD contains 2 CH domains (CH1 and CH2), followed by 24 Ig repeats, probably folded into antiparallel β-sheets. Two hinge domains separate the 24 Ig repeats into 2 rod domains (hinge 1: between Ig repeats 15 and 16 and hinge 2 between Ig repeats 23 and 24). Ig repeats 9 to 15 in rod-1 facilitate F-actin binding, whereas Ig repeats 16 to 23 interact with different partners. Dimerization occurs through Ig repeat 24. (A) FLNa interacts with the platelet receptor GPIbα through the Ig repeat 17, as well as with the recently described partners PACSIN2 and STIM1 in resting platelets. The interaction of FLNa with αIIbβ3 through the Ig repeat 21 was not demonstrated. (B) After platelet activation, FLNa interacts with the platelet receptors GPIbα and with the tyrosine kinase Syk involved in GPVI functions through the Ig repeats 17 and 5, respectively, as well as with PACSIN2 and STIM1. SOCE, store-operated calcium entry.