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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-11-3491.
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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4789-4796
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Mechanisms and implications of platelet discoid shape
Joseph E. Italiano, Jr,
Wolfgang Bergmeier,
Sanjay Tiwari,
Hervé Falet,
John H. Hartwig,
Karin M. Hoffmeister,
Patrick André,
Denisa D. Wagner, and
Ramesh A. Shivdasani
From the Division of Hematology and Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston; Center for Blood Research and Department of Pathology, Harvard Medical School, Boston; and Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.
The platelet marginal band consists of a single peripheral microtubule (MT) that is wound in 8 to 12 coils and maintains discoid cell shape. About 90% of  -tubulin in the marginal band is of the divergent, megakaryocyte (MK)/platelet-restricted 1 isoform. 1-tubulin–null mice show reduced proplatelet formation, thrombocytopenia, and platelet spherocytosis. Here, we show that structural abnormalities in resting 1-tubulin—/— platelets include frequent kinks and breaks in the marginal band. Platelets derived from mice lacking the transcription factor GATA1 show similar defects, probably as a direct consequence of absent 1-tubulin. 1-tubulin+/— platelets have normal ratios of -tubulin isotypes but the marginal band is half the normal thickness, which is sufficient to maintain elliptical cell shape. Thus, a threshold 50% or less of the normal amount of 1-tubulin is required to preserve marginal band integrity and cell shape. 1-tubulin—/— platelets have normal size and contents and show no defects in serotonin release or aggregation. Accordingly, the apparently isolated spherocytosis allows investigation of the role of discoid platelet shape in hemostasis. On agonist stimulation, the disorganized MTs in 1-tubulin—/— platelets fail to condense into central rings and instead are dispersed in short bundles and linear arrays. Nevertheless, intravital microscopy and flow chamber studies demonstrate full functionality of these spherocytic platelets under physiologic shear conditions. Together, these findings highlight the essential requirements of the MK/platelet-restricted 1-tubulin isoform in platelet structure and suggest that spherocytosis does not impair many aspects of platelet function.
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