Summary

A critical aspect of hemostasis is the release of clot-formingcomponents from the three intra-platelet stores: dense coregranules, a-granules and lysosomes. Exocytosis from thesegranules is mediated by soluble (SNAPs and NSF) and integralmembraneproteins (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 oftheir cognate syntaxin binding partner.To define the molecularmachinery required for platelet exocytosis, we analyzed plateletsfrom Munc18c heterozygous knockout mice.These plateletsshow a decrease in Munc18c but no apparent reduction inother secretory machinery components. No differences in the rates of aggregation or of secretion of [³H]-5HT (dense coregranules), platelet factor 4 (a-granules), or hexosaminidase(lysosomes) were detected between platelets from Munc18cheterozygous knockout or wild-type mice. The platelets alsoshow normal morphology. Contrary to a predicted requirementfor Munc18c in platelet secretion, data reported hereshow that reducing Munc18c levels does not substantially alterplatelet function.These data show that despite Munc18c’s rolein platelet secretion, the lack of a secretion defect may beattributed to compensation by other Munc18 isoforms or thatone allele is sufficient to maintain secretion under standardconditions.