TABLE 1.
Partner | Interacting domain | Relevance to platelet function | References |
---|---|---|---|
PKC* | FLNA Ig repeats 1–8 | FLNA mediates PKC activation and promotes β1 integrin activation and cell spreading | Kim and McCulloch, (2011) |
Syk | FLNA Ig repeat 5 | FLNA regulates ITAM and ITAM-like-mediated signaling | Falet et al. (2010); Falet, (2013) |
F-actin | FLNA Ig repeats 9–15 and Ig repeat 24 | FLNA stabilizes subcortical actin filaments; crosslinking F-actin into orthogonal networks | Nakamura et al. (2007) |
GPIbα | FLNA Ig repeat 17 with GPIbα cytoplasmic tail | FLNA modulates the interaction of GPIb-IX-V with vWF | Meyer et al. (1997); Williamson et al. (2002); Nakamura et al. (2006) |
PKA | FLNA Ig repeat 20 | PKA phosphorylates FLNA on S2152 to protect FLNA from calpain proteolysis | Chen and Stracher, (1989); Tirupula et al. (2015) |
PACSIN2 | FLNA Ig repeat 20 and PACSIN2-BAR domain | FLNA helps localization of PACSIN2 and regulates platelet membrane tubulation | Begonja et al. (2015) |
Trio (GEF)* | FLNA Ig repeats 21–24 with GEFD1 domain of Trio | FLNA-Trio interaction induces actin-based ruffling and remodeling of cytoskeletal actin | Bellanger et al. (2000) |
β3 integrin | FLNA Ig repeat 21 with β3 cytoplasmic tail | FLNA inhibits the activation of integrin αIIbβ3 by competitively blocking talin and kindlin-3 binding sites | Ma et al. (2007); Liu et al. (2015); Berrou et al. (2017) |
Migfilin | FLNA Ig repeat 21 | Migfilin releases the FLNA inhibition on integrin αIIbβ3 thus promoting activation | Lad et al. (2008); Zhou et al. (2020) |
Pak1* | FLNA Ig repeat 23 | Pak1 phosphorylates FLNA for cytoskeletal reorganization and regulates platelet activation downstream of GPVI signaling | Vadlamudi et al. (2002); Aslan et al. (2013) |
FilGAP* | FLNA Ig repeat 23 | FLNA-FilGAP interaction decreases Rac activity and protects cells against force-induced apoptosis | Shifrin et al. (2009); Ehrlicher et al. (2011) |
STIM1 | FLNA Ig repeat 24 | FLNA inhibits STIM1 clustering thereby downregulating store-operated calcium entry (SOCE) | Lopez et al. (2018) |
RalA* | FLNA Ig repeat 24 | FLNA-RalA interaction elicits actin-rich filopodia on cell surface; RalA regulates translocation of P-selectin | Ohta et al. (1999); Wersall et al. (2018) |
ROCK* | FLNA Ig repeat 24 with carboxy-terminal pleckstrin homology domain of Rock | FLNA interacts with ROCK to control actin remodeling | Ueda et al. (2003); Ohta et al. (2006); Kim and McCulloch, (2011) |
RhoA* | FLNA Ig repeat 24 | FLNA induces RhoA-mediated actomyosin contraction, modulates proplatelet formation, and controls megakaryocyte localization and migration | Ohta et al. (1999); Savoy and Ghosh, (2013); Sun et al. (2013); Dutting et al. (2017) |
Rac* | FLNA Ig repeat 24 | FLNA regulates Rac activation to control actin remodeling | Ohta et al. (1999) |
Cdc42* | FLNA Ig repeat 24 | FLNA-Cdc42 interaction regulates the actin cytoskeleton, and controls MK localization and migration | Ohta et al. (1999); Dutting et al. 2(017) |
*Proteins whose interactions with FLNA, have been shown in other (non-platelet) cell types.