Mechanisms and implications of platelet discoid shape. Blood 2003 Jun 15;101(12):4789-96
Date
02/15/2003Pubmed ID
12586623DOI
10.1182/blood-2002-11-3491Scopus ID
2-s2.0-0038792174 (requires institutional sign-in at Scopus site) 137 CitationsAbstract
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 beta-tubulin in the marginal band is of the divergent, megakaryocyte (MK)/platelet-restricted beta1 isoform. beta1-tubulin-null mice show reduced proplatelet formation, thrombocytopenia, and platelet spherocytosis. Here, we show that structural abnormalities in resting beta1-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 beta1-tubulin. beta1-tubulin+/- platelets have normal ratios of beta-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 beta1-tubulin is required to preserve marginal band integrity and cell shape. beta1-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 beta1-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 beta1-tubulin isoform in platelet structure and suggest that spherocytosis does not impair many aspects of platelet function.
Author List
Italiano JE Jr, Bergmeier W, Tiwari S, Falet H, Hartwig JH, Hoffmeister KM, André P, Wagner DD, Shivdasani RAAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelets
Cell Size
Cell Survival
DNA-Binding Proteins
Erythroid-Specific DNA-Binding Factors
GATA1 Transcription Factor
Hemorheology
Hemostasis
Male
Megakaryocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Microtubules
Platelet Activation
Platelet Aggregation
Transcription Factors
Tubulin
