NDLI: Munc18b/STXBP2 is required for platelet secretion

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Munc18b/STXBP2 is required for platelet secretion

Content Provider	Scilit
Author	Hawas, Rania Al Ren, Qiansheng Ye, Shaojing Karim, Zubair A. Filipovich, Alexandra H. Whiteheart, Sidney W.
Copyright Year	2012
Description	Platelets are vital for hemostasis because they release their granule contents in response to vascular damage. Platelet exocytosis is mediated by soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs), whose interactions are governed by regulators, eg, Sec/Munc18 proteins. These proteins chaperone syntaxin t-SNAREs and are required for exocytosis. Platelets contain 3 Munc18 isoforms: Munc18a, Munc18b, and Munc18c. We report that Munc18b is the major isoform and is required for platelet secretion. Familial hemophagocytic lymphohistiocytosis type 5 (FHL5) is caused by defects in the Munc18b/STXBP2 gene. We confirm a previous report showing that platelets from FHL5 patients have defective secretion. Serotonin, ADP/ATP, and platelet factor 4 release was profoundly affected in the 2 biallelic patients and partially in a heterozygous patient. Release of lysosomal contents was only affected in the biallelic platelets. Platelets from the FHL5 biallelic patients showed decreased Munc18b and syntaxin-11 levels were significantly reduced; other syntaxins were unaffected. Munc18b formed complexes with syntaxin-11, SNAP-23, and vesicle-associated membrane protein-8 in human platelets. Other potential secretion regulators, Munc13-4 and Rab27, were also found associated. These data demonstrate a key role for Munc18b, perhaps as a limiting factor, in platelet exocytosis and suggest that it regulates syntaxin-11.
Related Links	https://ashpublications.org/blood/article-pdf/120/12/2493/984456/zh803812002493.pdf
Ending Page	2500
Page Count	8
Starting Page	2493
DOI	10.1182/blood-2012-05-430629
Journal	Blood
Issue Number	12
Volume Number	120
Language	English
Publisher	American Society of Hematology
Publisher Date	2012-09-20
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Proteins Platelet Secretion Snares Defects Biallelic Syntaxin Fhl5 Munc18b/stxbp2 Journal: Blood (Vol- 121, Issue- 12)
Content Type	Text
Resource Type	Article

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