Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release

Todd D. Schraw, Garland L. Crawford, Qiansheng Ren, Wangsun Choi, Debbie C. Thurmond, Jeffrey E. Pessin, Sidney W. Whiteheart

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 integral-membrane 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.

Original languageEnglish (US)
Pages (from-to)829-837
Number of pages9
JournalThrombosis and Haemostasis
Volume92
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Blood Platelets
Exocytosis
SNARE Proteins
Lysosomes
Munc18 Proteins
Qa-SNARE Proteins
Secretory Component
Platelet Factor 4
Hexosaminidases
Hemostasis
Knockout Mice
Protein Isoforms
Membrane Proteins
Alleles

Keywords

  • Munc18
  • Platelets
  • Secretion
  • SNARE
  • Syntaxin

ASJC Scopus subject areas

  • Hematology

Cite this

Schraw, T. D., Crawford, G. L., Ren, Q., Choi, W., Thurmond, D. C., Pessin, J. E., & Whiteheart, S. W. (2004). Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release. Thrombosis and Haemostasis, 92(4), 829-837. https://doi.org/TH04-04-0263

Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release. / Schraw, Todd D.; Crawford, Garland L.; Ren, Qiansheng; Choi, Wangsun; Thurmond, Debbie C.; Pessin, Jeffrey E.; Whiteheart, Sidney W.

In: Thrombosis and Haemostasis, Vol. 92, No. 4, 10.2004, p. 829-837.

Research output: Contribution to journalArticle

Schraw, TD, Crawford, GL, Ren, Q, Choi, W, Thurmond, DC, Pessin, JE & Whiteheart, SW 2004, 'Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release', Thrombosis and Haemostasis, vol. 92, no. 4, pp. 829-837. https://doi.org/TH04-04-0263
Schraw, Todd D. ; Crawford, Garland L. ; Ren, Qiansheng ; Choi, Wangsun ; Thurmond, Debbie C. ; Pessin, Jeffrey E. ; Whiteheart, Sidney W. / Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release. In: Thrombosis and Haemostasis. 2004 ; Vol. 92, No. 4. pp. 829-837.
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