Rasa3 Controls Megakaryocyte Rap1 Activation, Integrin Signaling and Differentiation into Proplatelet

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Megakaryocytes are the bone marrow cellular precursors of circulating blood platelets and give rise to nascent platelets by forming branching filaments called proplatelets. Terminal differentiation of round megakaryocytes into branched proplatelet forming megakaryocytes is a complex cytoskeletal-driven process which is affected in rare human familial thrombocytopenias. Interactions of megakaryocytes with extracellular matrix proteins are essential in this process since constitutive megakaryocyte integrin activity caused by specific mutations in ITGA2B or ITGB3 genes encoding for extracellular matrix protein receptors may result in abnormal adherent megakaryocytes, defect in proplatelet formation and thrombocytopenia. Here, we show that Rasa3, a GTPase activating protein of the GAP1 family, controls Rap1 activation and integrin signaling during megakaryocyte differentiation. We found that Rasa3 catalytic inactivation in mice altered megakaryocyte development, adherence, migration, actin cytoskeleton organization and differentiation into proplatelet. Thus, these mice presented a severe thrombocytopenia, bleeding and anemia.

Vyšlo v časopise: Rasa3 Controls Megakaryocyte Rap1 Activation, Integrin Signaling and Differentiation into Proplatelet. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004420
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004420

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