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Review
. 2019 Jul 16;20(14):3484.
doi: 10.3390/ijms20143484.

Tubulin in Platelets: When the Shape Matters

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Free PMC article
Review

Tubulin in Platelets: When the Shape Matters

Ernesto José Cuenca-Zamora et al. Int J Mol Sci. .
Free PMC article

Erratum in

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.

Keywords: Platelet; cytoskeleton; neonatal; platelets activation; post-translational modification; tubulin.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Megakaryocytes and proplatelets [37]. Human primary megakaryocytes and proplatelets derived from CD34+ hematopoietic stem cells progenitors obtained from cord blood (CB). At day 14 of culture, megakaryocytes show proplatelet (pointed with arrows) formation. DNA (DAPI, purple-blue), α-tubulin (green) and actin (red) staining.
Figure 2
Figure 2
Microtubules coiling during platelet activation.
Figure 3
Figure 3
Platelets under resting and stimulation conditions. (A) A schematic representation of granule reorganization during platelet activation. (B) Neonatal and adult representative platelet ultrastructure images, obtained by electron microscope with a magnification of 9700×. Granule centralization, before and after stimulation, was quantified in 50 sections per sample (3 samples per group), and per state (basal and stimulated). Statistical analysis showed differences in granule distance to the centroid in adult basal platelets as compared to 10 µM Thrombin receptor agonist peptide-6 (TRAP)-stimulated adult platelets (p < 0.01). No differences were found, by contrast, between basal and stimulated neonatal platelets or between quiescent adult and neonatal platelets. Granule centralization was measured using the Leica QWin Pro v3 Software (Leica Microsystems).
Figure 4
Figure 4
Neonatal platelets display a reduced expression of β1-tubulin but an overexpression of other isoforms (TUBB2A and TUBB), allowing a normal marginal band. (A) TUBB1 mRNA level measured by quantitative real time qRT-PCR and normalized with respect to ACTB (n = 21/group). (B) Quantification of β1-tubulin protein levels by immunoblotting. Western blot pictures shown are representative images cropped from two gels performed at the same time and under the same conditions (n = 15 samples/group). Quantification was performed by densitometric analysis using the ImageJ program, and was normalized to β-Actin. (C,D) Microscopy of adult and neonatal platelet marginal bands using α-tubulin immunofluorescence in adhered platelets on poly-l-lysine. (E,F) Quantification of TUBB2A and TUBB mRNA levels by qRT-PCR (n ≥ 10 samples per group). ** p < 0.01. Taken from [63] with permission.

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