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- Title
Syntaxin11 serves as a t- SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes.
- Authors
Halimani, Mahantappa; Pattu, Varsha; Marshall, Misty R.; Chang, Hsin Fang; Matti, Ulf; Jung, Martin; Becherer, Ute; Krause, Elmar; Hoth, Markus; Schwarz, Eva C.; Rettig, Jens
- 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.
- Publication
European Journal of Immunology, 2014, Vol 44, Issue 2, p573
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201344011