Syntaxin11 serves as a t-SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes

34Citations
Citations of this article
48Readers
Mendeley users who have this article in their library.

This article is free to access.

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. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cite

CITATION STYLE

APA

Halimani, M., Pattu, V., Marshall, M. R., Chang, H. F., Matti, U., Jung, M., … Rettig, J. (2014). Syntaxin11 serves as a t-SNARE for the fusion of lytic granules in human cytotoxic T lymphocytes. European Journal of Immunology, 44(2), 573–584. https://doi.org/10.1002/eji.201344011

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free