Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells

Anne Chauveau, Anne Aucher, Philipp Eissmann, Eric Vivier, Daniel M. Davis

    Research output: Contribution to journalArticlepeer-review


    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.
    Original languageEnglish
    Pages (from-to)5545-5550
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number12
    Publication statusPublished - 23 Mar 2010


    • Cell activation
    • Cell motility
    • Cytotoxicity
    • Immune synapses
    • Intercellular communication


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