Disrupted filamin A/α_IIbβ₃ interaction induces macrothrombocytopenia by increasing RhoA activity.

ABSTRACT: Filamin A (FLNa) links the cell membrane with the cytoskeleton and is central in several cellular processes. Heterozygous mutations in the X-linked FLNA gene are associated with a large spectrum of conditions, including macrothrombocytopenia, called filaminopathies. Using an isogenic pluripotent stem cell model derived from patients, we show that the absence of the FLNa protein in megakaryocytes (MKs) leads to their incomplete maturation, particularly the inability to produce proplatelets. Reduction in proplatelet formation potential is associated with a defect in actomyosin contractility, which results from inappropriate RhoA activation. This dysregulated RhoA activation was observed when MKs were plated on fibrinogen but not on other matrices (fibronectin, vitronectin, collagen 1,

SUBMITTER: Donada A 

PROVIDER: S-EPMC6484462 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature