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The size of activating and inhibitory killer Ig-like receptor nanoclusters is controlled by the transmembrane sequence and affects signaling

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dc.contributor.authorOszmiana, A.
dc.contributor.authorWilliamson, D.J.
dc.contributor.authorCordoba, S.P.
dc.contributor.authorMorgan, D.J.
dc.contributor.authorKennedy, P.R.
dc.contributor.authorStacey, K.
dc.contributor.authorDavis, D.M.
dc.date.issued2016
dc.descriptionData source: Figures and tables, https://doi.org/10.1016/j.celrep.2016.04.075
dc.description.abstractSuper-resolution microscopy has revealed that immune cell receptors are organized in nanoscale clusters at cell surfaces and immune synapses. However, mechanisms and functions for this nanoscale organization remain unclear. Here, we used super-resolution microscopy to compare the surface organization of paired killer Ig-like receptors (KIR), KIR2DL1 and KIR2DS1, on human primary natural killer cells and cell lines. Activating KIR2DS1 assembled in clusters two-fold larger than its inhibitory counterpart KIR2DL1. Site-directed mutagenesis established that the size of nanoclusters is controlled by transmembrane amino acid 233, a lysine in KIR2DS1. Super-resolution microscopy also revealed two ways in which the nanoscale clustering of KIR affects signaling. First, KIR2DS1 and DAP12 nanoclusters are juxtaposed in the resting cell state but coalesce upon receptor ligation. Second, quantitative super-resolution microscopy revealed that phosphorylation of the kinase ZAP-70 or phosphatase SHP-1 is favored in larger KIR nanoclusters. Thus, the size of KIR nanoclusters depends on the transmembrane sequence and affects downstream signaling.
dc.identifier.citationCell reports, 2016; 15(9):1957-1972
dc.identifier.doi10.1016/j.celrep.2016.04.075
dc.identifier.issn2211-1247
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/11541.2/128084
dc.language.isoen
dc.publisherElsevier
dc.relation.fundingMedical Research Council G1001044
dc.relation.fundingWellcome Trust Investigator Award 110091
dc.relation.fundingUniversity of Manchester
dc.rightsCopyright 2016 The Authors. This article is available under the terms of the Creative Commons Attribution License (CC BY). You may copy and distribute the article, create extracts, abstracts and new works from the article, alter and revise the article, text or data mine the article and otherwise reuse the article commercially (including reuse and/or resale of the article) without permission from Elsevier. You must give appropriate credit to the original work, together with a link to the formal publication through the relevant DOI and a link to the Creative Commons user license above. You must indicate if any changes are made but not in any way that suggests the licensor endorses you or your use of the work. (https://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1016/j.celrep.2016.04.075
dc.subjectimmunoglobulin-like receptors
dc.subjectcell immune synapse
dc.subjectNK cells
dc.subjectplasma membrane
dc.subjecttyrosine phosphorylation
dc.subjectKIR2DL1
dc.subjectKIR2DS1
dc.titleThe size of activating and inhibitory killer Ig-like receptor nanoclusters is controlled by the transmembrane sequence and affects signaling
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916149092601831

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