期刊
BLOOD
卷 134, 期 16, 页码 1279-1288出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019000014
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资金
- INSERM
- Fondation pour la Recherche Medicale [LPC20170637458]
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, the megakaryocytic 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 alpha IIb beta 3 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 alpha IIb beta 3, 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.
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