engleski

Molecular mechanisms of megakaryocyte and platelet development

Platelets are essential for haemostasis as they recognize and bind to the site of vessel injury, contribute to angiogenesis and wound healing. Platelets are produced by precursor cells called megakaryocytes that reside in the bone marrow. Major cytokine that regulates megakaryocyte and platelet formation is thrombopoetin. Megakaryocytes develop from haematopoetic stem cells in the process of megakaryopeisis and undergo endomitosis, maturation of demarcation membrane system and granule formation. Production of platelets continues in the process of thrombopoeisis and requires series of complex events through remodeling of megakaryocyte cytoskeleton that results in the release of thousands of platelets from one megakaryocyte. Megakaryocyte extend long, branching processes called proplatelets into sinusoidal blood vessels. Pre-platelets are being released from the ends of proplatelets that are considerably larger than platelets. These structures have the ability to convert into barbell shaped proplatelets and finally mature into two platelets. Abnormalities in these processes can lead to clinically significant disorders. In this review we will focus on different factors that impact megakaryocyte development, proplatelet formation and platelet release. We will present new studies on the mechanism that control platelet numbers in circulation, cytoskeletal contribution in megakaryopoeisis, and specifically the role of filamin A in biogenesis, function and lifespan of platelets.

platelets, megakaryocytes, proplatelets, cytoskeleton, filamin A

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