Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release.
A critical aspect of hemostasis is the release of clot-forming components from the three intra-platelet stores: dense core granules, alpha-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 [(3)H]-5HT (dense core granules), platelet factor 4 (alpha-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.
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Todd D
TD
Schraw
Garland L
GL
Crawford
Qiansheng
Q
Ren
Wangsun
W
Choi
Debbie C
DC
Thurmond
Jeffery
J
Pessin
Sidney W
SW
Whiteheart
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D006579:Heterozygote; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010974:Platelet Aggregation; D020033:Protein Isoforms; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*
D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C497943:Stxbp3 protein, mouse; D033921:Vesicular Transport Proteins