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Membrane nanotubes: dynamic long-distance connections between animal cells
Nature Reviews Molecular Cell Biologyvolume 9, pages431–436 (2008)Cite this article
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Abstract
Membrane nanotubes are transient long-distance connections between cells that can facilitate intercellular communication (for example, by trafficking vesicles or transmitting calcium-mediated signals), but they can also contribute to pathologies (for example, by directing the spread of viruses). Recent data have revealed considerable heterogeneity in their structures, processes of formation and functional properties, in part dependent on the cell types involved. Despite recent progress in this young research field, further research is sorely needed.
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References
Chhabra, E. S. & Higgs, H. N. The many faces of actin: matching assembly factors with cellular structures.Nature Cell Biol.9, 1110–1121 (2007).
Rustom, A., Saffrich, R., Markovic, I., Walther, P. & Gerdes, H. H. Nanotubular highways for intercellular organelle transport.Science303, 1007–1010 (2004).
Onfelt, B., Nedvetzki, S., Yanagi, K. & Davis, D. M. Cutting edge: membrane nanotubes connect immune cells.J. Immunol.173, 1511–1513 (2004).
Watkins, S. C. & Salter, R. D. Functional connectivity between immune cells mediated by tunneling nanotubules.Immunity23, 309–318 (2005).
Onfelt, B. et al. Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria.J. Immunol.177, 8476–8483 (2006).
Sowinski, S. et al. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.Nature Cell Biol.10, 211–219 (2008).
Gerdes, H. H., Bukoreshtliev, N. V. & Barroso, J. F. Tunneling nanotubes: a new route for the exchange of components between animal cells.FEBS Lett.581, 2194–2201 (2007).
Stinchcombe, J. C., Bossi, G., Booth, S. & Griffiths, G. M. The immunological synapse of CTL contains a secretory domain and membrane bridges.Immunity15, 751–761 (2001).
Eriksson, M. et al. Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.J. Exp. Med.190, 1005–1012 (1999).
Roda-Navarro, P. et al. Dynamic redistribution of the activating 2B4/SAP complex at the cytotoxic NK cell immune synapse.J. Immunol.173, 3640–3646 (2004).
Pontes, B. et al. Structure and elastic properties of tunneling nanotubes.Eur. Biophys. J.37, 121–129 (2008).
Kiesel, M. et al. Swelling-activated pathways in human T-lymphocytes studied by cell volumetry and electrorotation.Biophys. J.90, 4720–4729 (2006).
Raucher, D. & Sheetz, M. P. Characteristics of a membrane reservoir buffering membrane tension.Biophys. J.77, 1992–2002 (1999).
Schmidtke, D. W. & Diamond, S. L. Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow.J. Cell Biol.149, 719–730 (2000).
Williams, G. S. et al. Membranous structures transfer cell surface proteins across NK cell immune synapses.Traffic8, 1190–1204 (2007).
Shao, J. Y. & Hochmuth, R. M. Micropipette suction for measuring piconewton forces of adhesion and tether formation from neutrophil membranes.Biophys. J.71, 2892–2901 (1996).
Zhang, X., Wojcikiewicz, E. & Moy, V. T. Force spectroscopy of the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction.Biophys. J.83, 2270–2279 (2002).
Zhang, X., Wojcikiewicz, E. P. & Moy, V. T. Dynamic adhesion of T lymphocytes to endothelial cells revealed by atomic force microscopy.Exp. Biol. Med. (Maywood)231, 1306–1312 (2006).
Dai, J. & Sheetz, M. P. Membrane tether formation from blebbing cells.Biophys. J.77, 3363–3370 (1999).
Sheetz, M. P. Cell control by membrane–cytoskeleton adhesion.Nature Rev. Mol. Cell Biol.2, 392–396 (2001).
Sheetz, M. P. & Dai, J. Modulation of membrane dynamics and cell motility by membrane tension.Trends Cell Biol.6, 85–89 (1996).
Vidulescu, C., Clejan, S. & O'Connor K. C. Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells.J. Cell. Mol. Med.8, 388–396 (2004).
Iglic, A., Hagerstrand, H., Bobrowska-Hagerstrand, M., Arrigler, V. & Kraij-Iglic, V. Possible role of phospholipid nanotubes in directed transport of membrane vesicles.Physics Letters A310, 493–497 (2003).
Spees, J. L., Olson, S. D., Whitney, M. J. & Prockop, D. J. Mitochondrial transfer between cells can rescue aerobic respiration.Proc. Natl Acad. Sci. USA103, 1283–1288 (2006).
Cilia, M. L. & Jackson, D. Plasmodesmata form and function.Curr. Opin. Cell Biol.16, 500–506 (2004).
Holdaway-Clarke, T. L., Walker, N. A., Hepler, P. K. & Overall, R. L. Physiological elevations in cytoplasmic free calcium by cold or ion injection result in transient closure of higher plant plasmodesmata.Planta210, 329–335 (2000).
Davis, D. M. Intercellular transfer of cell-surface proteins is common and can affect many stages of an immune response.Nature Rev. Immunol.7, 238–243 (2007).
Sprent, J. Swapping molecules during cell–cell interactions.Sci. STKE273, pe8 (2005).
Hudrisier, D. & Bongrand, P. Intercellular transfer of antigen-presenting cell determinants onto T cells: molecular mechanisms and biological significance.FASEB J.16, 477–486 (2002).
Roda-Navarro, P. & Reyburn, H. T. Intercellular protein transfer at the NK cell immune synapse: mechanisms and physiological significance.FASEB J.21, 1636–1646 (2007).
Huang, J. F. et al. TCR-mediated internalization of peptide-MHC complexes acquired by T cells.Science286, 952–954 (1999).
McCann, F. E., Eissmann, P., Onfelt, B., Leung, R. & Davis, D. M. The activating NKG2D ligand MHC class I-related chain A transfers from target cells to NK cells in a manner that allows functional consequences.J. Immunol.178, 3418–3426 (2007).
Fevrier, B. & Raposo, G. Exosomes: endosomal-derived vesicles shipping extracellular messages.Curr. Opin. Cell Biol.16, 415–421 (2004).
Joly, E. & Hudrisier, D. What is trogocytosis and what is its purpose?Nature Immunol.4, 815 (2003).
Rorth, P. Communication by touch: role of cellular extensions in complex animals.Cell112, 595–598 (2003).
Johnson, D. C. & Huber, M. T. Directed egress of animal viruses promotes cell-to-cell spread.J. Virol.76, 1–8 (2002).
Sourisseau, M., Sol-Foulon, N., Porrot, F., Blanchet, F. & Schwartz, O. Inefficient human immunodeficiency virus replication in mobile lymphocytes.J. Virol.81, 1000–1012 (2007).
Marsh, M. & Helenius, A. Virus entry: open sesame.Cell124, 729–740 (2006).
Igakura, T. et al. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton.Science299, 1713–1716 (2003).
Chen, P., Hubner, W., Spinelli, M. A. & Chen, B. K. Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses.J. Virol.81, 12582–12595 (2007).
Jolly, C., Kashefi, K., Hollinshead, M. & Sattentau, Q. J. HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse.J. Exp. Med.199, 283–293 (2004).
Davis, D. M. & Dustin, M. L. What is the importance of the immunological synapse?Trends Immunol.25, 323–327 (2004).
La Boissiere, S., Izeta, A., Malcomber, S. & O'Hare, P. Compartmentalization of VP16 in cells infected with recombinant herpes simplex virus expressing VP16-green fluorescent protein fusion proteins.J. Virol.78, 8002–8014 (2004).
Smith, G. L., Murphy, B. J. & Law, M. Vaccinia virus motility.Annu. Rev. Microbiol.57, 323–342 (2003).
Favoreel, H. W., Van Minnebruggen, G., Adriaensen, D. & Nauwynck, H. J. Cytoskeletal rearrangements and cell extensions induced by the US3 kinase of an aherpesvirus are associated with enhanced spread.Proc. Natl Acad. Sci. USA102, 8990–8995 (2005).
Sherer, N. M. et al. Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission.Nature Cell Biol.9, 310–315 (2007).
Hope, T. J. Bridging efficient viral infection.Nature Cell Biol.9, 243–244 (2007).
Brass, A. L. et al. Identification of host proteins required for HIV infection through a functional genomic screen.Science319, 921–926 (2008).
Sjostrom, A. et al. Acquisition of external major histocompatibility complex class I molecules by natural killer cells expressing inhibitory Ly49 receptors.J. Exp. Med.194, 1519–1530 (2001).
Smyth, L. A., Herrera, O. B., Golshayan, D., Lombardi, G. & Lechler, R. I. A novel pathway of antigen presentation by dendritic and endothelial cells: implications for allorecognition and infectious diseases.Transplantation82 (Suppl. 1), S15–S18 (2006).
Hsiung, F., Ramirez-Weber, F. A., Iwaki, D. D. & Kornberg, T. B. Dependence ofDrosophila wing imaginal disc cytonemes on Decapentaplegic.Nature437, 560–563 (2005).
Chinnery, H. R., Pearlman, E. & McMenamin, P. G. Membrane nanotubesin vivo: a feature of MHC class II+ cells in the mouse cornea.J. Immunol. (in the press).
Miller, J., Fraser, S. E. & McClay, D. Dynamics of thin filopodia during sea urchin gastrulation.Development121, 2501–2511 (1995).
Salas-Vidal, E. & Lomeli, H. Imaging filopodia dynamics in the mouse blastocyst.Dev. Biol.265, 75–89 (2004).
Baluska, F., Volkmann, D. & Barlow, P. W.Cell–cell channels (Landes Bioscience and Springer Science, New York, 2006).
Hodneland, E. et al. Automated detection of tunneling nanotubes in 3D images.Cytometry A69, 961–972 (2006).
Koster, G., Cacciuto, A., Derenyi, I., Frenkel, D. & Dogterom, M. Force barriers for membrane tube formation.Phys. Rev. Lett.94, 068101 (2005).
Shibata, Y., Voeltz, G. K. & Rapoport, T. A. Rough sheets and smooth tubules.Cell126, 435–439 (2006).
Farsad, K. & De Camilli, P. Mechanisms of membrane deformation.Curr. Opin. Cell Biol.15, 372–381 (2003).
McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling.Nature438, 590–596 (2005).
Itoh, T. & De Camilli, P. BAR, F-BAR (EFC) and ENTH/ANTH domains in the regulation of membrane-cytosol interfaces and membrane curvature.Biochim. Biophys. Acta1761, 897–912 (2006).
Takei, K., Slepnev, V. I., Haucke, V. & De Camilli, P. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis.Nature Cell Biol.1, 33–39 (1999).
Mattila, P. K. et al. Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism.J. Cell Biol.176, 953–964 (2007).
Roux, A. et al. Role of curvature and phase transition in lipid sorting and fission of membrane tubules.EMBO J.24, 1537–1545 (2005).
Roda-Navarro, P., Vales-Gomez, M., Chisholm, S. E. & Reyburn, H. T. Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function.Proc. Natl Acad. Sci. USA103, 11258–11263 (2006).
Lehmann, M. J., Sherer, N. M., Marks, C. B., Pypaert, M. & Mothes, W. Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells.J. Cell Biol.170, 317–325 (2005).
Karlsson, M. et al. Biomimetic nanoscale reactors and networks.Annu. Rev. Phys. Chem.55, 613–649 (2004).
Bauer, B., Davidson, M. & Orwar, O. Direct reconstitution of plasma membrane lipids and proteins in nanotube-vesicle networks.Langmuir22, 9329–9332 (2006).
Tokarz, M., Hakonen, B., Dommersnes, P., Orwar, O. & Akerman, B. Electrophoretic transport of latex particles in lipid nanotubes.Langmuir23, 7652–7658 (2007).
Acknowledgements
We thank H. Chinnery, P. McMenamin, I. Rupp, G. Pradel and A. Chauveau for sharing unpublished observations, B. Önfelt and O. Ces for useful discussions, members of our laboratory for comments on the manuscript and N. Powell for help in preparing the figures. Research in our laboratory is funded by the Medical Research Council, the Biotechnology and Biological Science Research Council, a Lister Research Institute Fellowship and a Royal Society Wolfson Research Merit Award. S. S. is funded by a Wellcome Trust studentship.
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Daniel M. Davis and Stefanie Sowinski are at the Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, UK.,
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Davis, D., Sowinski, S. Membrane nanotubes: dynamic long-distance connections between animal cells.Nat Rev Mol Cell Biol9, 431–436 (2008). https://doi.org/10.1038/nrm2399
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