Thromb Haemost 2011; 105(05): 855-863
DOI: 10.1160/TH10-08-0536
Platelets and Blood Cells
Schattauer GmbH

Rare homozygous status of P43 β1-tubulin polymorphism causes alterations in platelet ultrastructure

Leyre Navarro-Núñez*yen
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Raúl Teruelyen
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Ana Isabel Antón
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Paquita Nurden
2   Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d‘Innovation Biomédicale, Hôpital Cardiologique, Pessac, France
,
Irene Martínez-Martínez
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
María Luisa Lozano
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
José Rivera
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Javier Corral
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Diego Mezzano
3   Pontificia Universidad Católica de Chile, Santiago, Chile
,
Vicente Vicente
1   Centro Regional de Hemodonación, University of Murcia, Spain
,
Constantino Martínez
1   Centro Regional de Hemodonación, University of Murcia, Spain
› Institutsangaben

Financial support: L. N-N holds a Post-Doctoral grant from Ministerio de Ciencia e Innovación and R.T holds FPI fellowships from Ministerio de Ciencia e Innovación (BES-2007–16973). C.M is an investigator from Fundación para la Formación e Investigación Sanitarias de la Región de Murcia (FFIS). This work was supported by an EMBO short term fellowship (ASTF 385–2008) and research grants from ISCIII and FEDER (PI08/1506, EMER07/035), ISCIII (Red RECAVA RD06/0014/0039), and Fundación Séneca (07703/GERM/07).
Weitere Informationen

Publikationsverlauf

Received: 18. August 2010

Accepted after major revision: 03. Februar 2011

Publikationsdatum:
28. November 2017 (online)

Preview

Summary

β1-tubulin is the main constituent of the platelet marginal band and studies with deficient mice showed that it maintains discoid shape and it is required for normal platelet formation. TUBB1 Q43P polymorphism is associated with decreased β1-tubulin expression, diminished platelet reactivity, and partial loss of discoid shape in heterozygous carriers. However, to date no studies have been carried out on homozygous PP individuals. Our study included 19 subjects genotyped for TUBB1 Q43P polymorphism (4 QQ, 4 QP, and 2 PP). The two PP individuals were recruited after genotyping of 2073 individuals. Biochemical, microscopy, and molecular studies were performed. Real-time PCR showed ∼40% decrease in TUBB1 mRNA in the two PP individuals compared to four QQ subjects. Western blot analysis confirmed this reduction. Electron microscopy revealed a majority of normal discoid platelets in PP individuals, although platelets with loose, re-orientated or invaginated protofilaments, and an over-developed open canalicular system were observed. Such abnormalities were not observed in QQ subjects. Morphometric analyses showed no differences between PP and QQ individuals. Immunofluorescence confirmed the presence of a normal marginal band in a majority of platelets from PP subjects. Interestingly, both PP subjects had a 40% lower platelet count than QP and QQ. TUBB1 Q43P polymorphism in homozygosity mildly affects platelet ultrastructure and our data further suggest that high levels of β1-tubulin might not be critical to sustain platelet discoid shape.

* Present address: Birmingham Platelet Group, Centre for Cardiovascular Sciences, Institute of Biomedical Research, The College of Medical and Dental Sciences, University of Birmingham, United Kingdom.


yen Both authors equally contributed to the study.