title: Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells.
abstract: Membrane nanotubes are membranous tethers that physically link cell bodies over long distances. Here, we present evidence that nanotubes allow human natural killer (NK) cells to interact functionally with target cells over long distances. Nanotubes were formed when NK cells contacted target cells and moved apart. The frequency of nanotube formation was dependent on the number of receptor/ligand interactions and increased on NK cell activation. Most importantly, NK cell nanotubes contained a submicron scale junction where proteins accumulated, including DAP10, the signaling adaptor that associates with the activating receptor NKG2D, and MHC class I chain-related protein A (MICA), a cognate ligand for NKG2D, as occurs at close intercellular synapses between NK cells and target cells. Quantitative live-cell fluorescence imaging suggested that MICA accumulated at small nanotube synapses in sufficient numbers to trigger cell activation. In addition, tyrosine-phosphorylated proteins and Vav-1 accumulated at such junctions. Functionally, nanotubes could aid the lysis of distant target cells either directly or by moving target cells along the nanotube path into close contact for lysis via a conventional immune synapse. Target cells moving along the nanotube path were commonly polarized such that their uropods faced the direction of movement. This is the opposite polarization than for normal cell migration, implying that nanotubes can specifically drive target cell movement. Finally, target cells that remained connected to an NK cell by a nanotube were frequently lysed, whereas removing the nanotube using a micromanipulator reduced lysis of these target cells.
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Chauveau
authors.forename: Anne
authors.initials: A
authors.lastname: Aucher
authors.forename: Philipp
authors.initials: P
authors.lastname: Eissmann
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000000981:diagnostic imaging* / Q000276:immunology*; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D043942:Nanotubes / Q000648:ultrastructure*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014463:Ultrasonography
chemical_list: C120528:HCST protein, human; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D051567:Proto-Oncogene Proteins c-vav; D011971:Receptors, Immunologic; C496618:VAV1 protein, human