TY - JOUR
T1 - Filamin A
T2 - Key actor in platelet biology
AU - Rosa, Jean Philippe
AU - Raslova, Hana
AU - Bryckaert, Marijke
N1 - Publisher Copyright:
© 2019 American Society of Hematology. All rights reserved.
PY - 2019/10/17
Y1 - 2019/10/17
N2 - Filamins (FLNs) are large dimeric actin-binding proteins that regulate actin cytoskeleton remodeling. In addition, FLNs serve as scaffolds for signaling proteins, such as tyrosine kinases, GTPases, or phosphatases, as well as for adhesive receptors, such as integrins. Thus, they connect adhesive receptors to signaling pathways and to cytoskeleton. There are 3 isoforms of FLN (filamin a [FLNa], FLNb, FLNc) that originate from 3 homologous genes. FLNa has been the recent focus of attention because its mutations are responsible for a wide spectrum of defects called filaminopathies A, affecting brain (peri-ventricular nodular heterotopia), heart (valve defect), skeleton, gastrointestinal tract, and,more recently, themegakaryocytic lineage. This review will focus on the physiological and pathological roles of FLNa in platelets. Indeed, FLNa mutations alter platelet production from their bone marrow precursors, the megakaryocytes, yielding giant platelets in reduced numbers (macrothrombocytopenia). In platelets per se, FLNa mutations may lead to impaired aIIbb3 integrin activation or in contrast, increased aIIbb3 activation, potentially enhancing the risk of thrombosis. Experimental work delineating the interaction of FLNa with its platelet partners, including aIIbb3, the von Willebrand factor receptor GPIb-IX-V, the tyrosine kinase Syk, and the signaling pathway of the collagen receptor GPVI, will also be reviewed.
AB - Filamins (FLNs) are large dimeric actin-binding proteins that regulate actin cytoskeleton remodeling. In addition, FLNs serve as scaffolds for signaling proteins, such as tyrosine kinases, GTPases, or phosphatases, as well as for adhesive receptors, such as integrins. Thus, they connect adhesive receptors to signaling pathways and to cytoskeleton. There are 3 isoforms of FLN (filamin a [FLNa], FLNb, FLNc) that originate from 3 homologous genes. FLNa has been the recent focus of attention because its mutations are responsible for a wide spectrum of defects called filaminopathies A, affecting brain (peri-ventricular nodular heterotopia), heart (valve defect), skeleton, gastrointestinal tract, and,more recently, themegakaryocytic lineage. This review will focus on the physiological and pathological roles of FLNa in platelets. Indeed, FLNa mutations alter platelet production from their bone marrow precursors, the megakaryocytes, yielding giant platelets in reduced numbers (macrothrombocytopenia). In platelets per se, FLNa mutations may lead to impaired aIIbb3 integrin activation or in contrast, increased aIIbb3 activation, potentially enhancing the risk of thrombosis. Experimental work delineating the interaction of FLNa with its platelet partners, including aIIbb3, the von Willebrand factor receptor GPIb-IX-V, the tyrosine kinase Syk, and the signaling pathway of the collagen receptor GPVI, will also be reviewed.
UR - http://www.scopus.com/inward/record.url?scp=85074428173&partnerID=8YFLogxK
U2 - 10.1182/blood.2019000014
DO - 10.1182/blood.2019000014
M3 - Review article
C2 - 31471375
AN - SCOPUS:85074428173
SN - 0006-4971
VL - 134
SP - 1279
EP - 1288
JO - Blood
JF - Blood
IS - 16
ER -