Abstract
Platelets are anuclear cells with a short lifespan that play an essential role in many pathophysiological processes, including haemostasis, inflammation, infection, vascular integrity, and metastasis. Billions of platelets are produced daily from megakaryocytes (platelet precursors). Despite this high production, the number of circulating platelets is stable and, under resting conditions, they maintain their typical discoid shape thanks to cytoskeleton proteins. The activation of platelets is associated with dynamic and rapid changes in the cytoskeleton. Two cytoskeletal polymer systems exist in megakaryocytes and platelets: actin filaments and microtubules, based on actin, and α- and β-tubulin heterodimers, respectively. Herein, we will focus on platelet-specific tubulins and their alterations and role of the microtubules skeleton in platelet formation (thrombopoiesis). During this process, microtubules mediate elongation of the megakaryocyte extensions (proplatelet) and granule trafficking from megakaryocytes to nascent platelets. In platelets, microtubules form a subcortical ring, the so-called marginal band, which confers the typical platelet discoid shape and is also responsible for changes in platelet morphology upon activation. Molecular alterations in the gene encoding β1 tubulin and microtubules post-translational modifications may result in quantitative or qualitative changes in tubulin, leading to altered cytoskeleton reorganization that may induce changes in the platelet number (thrombocytopenia), morphology or function. Consequently, β1-tubulin modifications may participate in pathological and physiological processes, such as development.
Highlights
Platelets, called thrombocytes, are membrane-bound cell fragments generated and released into the bloodstream as a result of fragmentation of larger precursor cells called megakaryocytes (MKs) that originate from hematopoietic stem cells [1]
In mouse, it has been described that members of the Ran-binding protein family, such as RanBP10, can play a crucial role both in maintaining the discoid shape in resting platelets and in platelet degranulation upon activation [31]
Based on an association study, we previously reported that β1-tubulin p.Q43P polymorphism is a weak risk factor for intracranial bleeding [58], but does not protect against acute coronary syndrome [59]
Summary
Called thrombocytes, are membrane-bound cell fragments generated and released into the bloodstream as a result of fragmentation of larger precursor cells called megakaryocytes (MKs) that originate from hematopoietic stem cells [1]. Upon damage to the vascular endothelium, sub-endothelial matrix proteins are exposed, such as collagen and von Willebrand Factor (vWF), which provides docking sites for platelet receptors such as glycoprotein (GP) VI and GP1bα, respectively The binding of these receptors to their ligands initiates a complex process, including several signal transduction cascades that promote platelet activation, shape change, spreading and degranulation, resulting in the recruitment of more platelets from the circulation into the platelet plug [2]. The activated platelet can serve as a support for interaction with coagulation factors and promote the formation of fibrin and platelet aggregate consolidation To trigger these biological functions, platelets undergo a characteristic pattern of morphological changes in response to different stimuli. Cytoskeleton is responsible for the shape changes associated with megakaryocyte maturation and proplatelet formation. We will point out how tubulin genetic variants and/or changes in tubulin expression levels may underlie a variety of platelets disorders or even physiological processes, such as development
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