Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6479
Keywords
-
Categories
Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Wellcome Trust
- University of Manchester Strategic Fund
- BBSRC
- Medical Research Council
- GlaxoSmithKline
- Biotechnology and Biological Sciences Research Council [BB/I013407/2] Funding Source: researchfish
- Medical Research Council [G0500563, G1001044] Funding Source: researchfish
- BBSRC [BB/I013407/2] Funding Source: UKRI
- MRC [G1001044, G0500563] Funding Source: UKRI
Ask authors/readers for more resources
Natural killer cells assess target cell health via interactions at the immune synapse (IS) that facilitates signal integration and directed secretion. Here we test whether the IS also functions as a gasket. Quantitative fluorescence microscopy of nanometer-scale dextrans within synapses formed by various effector-target cell conjugates reveal that molecules are excluded in a size-dependent manner at activating synapses. Dextran sized <= 4 nm move in and out of the IS, but access is significantly reduced (by >50%) for dextran sized 10-13 nm, and dextran >= 32 nm is almost entirely excluded. Depolymerization of F-actin abrogated exclusion. Unexpectedly, larger-sized dextrans are cleared as the IS assembles in a zipper-like manner. Monoclonal antibodies are also excluded from the IS but smaller single-domain antibodies are able to penetrate. Therefore, the IS can clear and exclude molecules above a size threshold, and drugs designed to target synaptic cytokines or cytotoxic proteins must fit these dimensions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available