Syntaxin11 serves as a t-SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes.
Eur J Immunol
; 44(2): 573-84, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24227526
ABSTRACT
CTLs kill target cells via fusion of lytic granules (LGs) at the immunological synapse (IS). Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) function as executors of exocytosis. The importance of SNAREs in CTL function is evident in the form of familial hemophagocytic lymphohistiocytosis type 4 that is caused by mutations in Syntaxin11 (Stx11), a Qa-SNARE protein. Here, we investigate the molecular mechanism of Stx11 function in primary human effector CTLs with high temporal and spatial resolution. Downregulation of endogenous Stx11 resulted in a complete inhibition of LG fusion that was paralleled by a reduction in LG dwell time at the IS. Dual color evanescent wave imaging suggested a sequential process, in which first Stx11 is transported to the IS through a subpopulation of recycling endosomes. The resulting Stx11 clusters at the IS then serve as a platform to mediate fusion of arriving LGs. We conclude that Stx11 functions as a t-SNARE for the final fusion of LG at the IS, explaining the severe phenotype of familial hemophagocytic lymphohistiocytosis type 4 on a molecular level.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Grânulos Citoplasmáticos
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Proteínas SNARE
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Proteínas Qa-SNARE
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha