Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release

Todd D. Schraw; Garland L. Crawford; Qiansheng Ren; Wangsun Choi; C. Thurmond Debbie; Jeffery Pessin; Sidney W. Whiteheart

doi:10.1160/TH04-04-0263

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 829-837
DOI: 10.1160/TH04-04-0263

Platelets and Blood Cells

Schattauer GmbH

Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release

Authors

Todd D. Schraw

¹Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
Garland L. Crawford

¹Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
Qiansheng Ren

¹Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
Wangsun Choi

¹Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
C. Thurmond Debbie

²Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana, USA
Jeffery Pessin

³The Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York, USA
Sidney W. Whiteheart

¹Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA

Abstract

Summary

A critical aspect of hemostasis is the release of clot-forming components from the three intra-platelet stores: dense core granules, α-granules and lysosomes. Exocytosis from these granules is mediated by soluble (SNAPs and NSF) and integralmembrane proteins (v- and t-SNAREs).Three SM (Sec1/Munc18) proteins are present in mouse platelets (Munc18a, 18b and 18c) and each potentially regulates exocytosis via modulation of their cognate syntaxin binding partner. To define the molecular machinery required for platelet exocytosis, we analyzed platelets from Munc18c heterozygous knockout mice. These platelets show a decrease in Munc18c but no apparent reduction in other secretory machinery components. No differences in the rates of aggregation or of secretion of [3H]-5HT (dense core granules), platelet factor 4 (α-granules), or hexosaminidase (lysosomes) were detected between platelets from Munc18c heterozygous knockout or wild-type mice. The platelets also show normal morphology. Contrary to a predicted requirement for Munc18c in platelet secretion, data reported here show that reducing Munc18c levels does not substantially alter platelet function. These data show that despite Munc18c’s role in platelet secretion, the lack of a secretion defect may be attributed to compensation by other Munc18 isoforms or that one allele is sufficient to maintain secretion under standard conditions.

Keywords

Munc18 - syntaxin - platelets - SNARE - secretion

Full Text

References

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