Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.

Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to under...

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Autores principales:	Alice C N Brown, Stephane Oddos, Ian M Dobbie, Juha-Matti Alakoskela, Richard M Parton, Philipp Eissmann, Mark A A Neil, Christopher Dunsby, Paul M W French, Ilan Davis, Daniel M Davis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c5fbcad5246744319db3103246e810fc
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spelling	oai:doaj.org-article:c5fbcad5246744319db3103246e810fc2021-11-04T05:33:00ZRemodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.1544-91731545-788510.1371/journal.pbio.1001152https://doaj.org/article/c5fbcad5246744319db3103246e810fc2011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931537/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F)-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM) to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC) polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.Alice C N BrownStephane OddosIan M DobbieJuha-Matti AlakoskelaRichard M PartonPhilipp EissmannMark A A NeilChristopher DunsbyPaul M W FrenchIlan DavisDaniel M DavisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 9, p e1001152 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Alice C N Brown Stephane Oddos Ian M Dobbie Juha-Matti Alakoskela Richard M Parton Philipp Eissmann Mark A A Neil Christopher Dunsby Paul M W French Ilan Davis Daniel M Davis Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
description	Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F)-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM) to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC) polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.
format	article
author	Alice C N Brown Stephane Oddos Ian M Dobbie Juha-Matti Alakoskela Richard M Parton Philipp Eissmann Mark A A Neil Christopher Dunsby Paul M W French Ilan Davis Daniel M Davis
author_facet	Alice C N Brown Stephane Oddos Ian M Dobbie Juha-Matti Alakoskela Richard M Parton Philipp Eissmann Mark A A Neil Christopher Dunsby Paul M W French Ilan Davis Daniel M Davis
author_sort	Alice C N Brown
title	Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
title_short	Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
title_full	Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
title_fullStr	Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
title_full_unstemmed	Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
title_sort	remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/c5fbcad5246744319db3103246e810fc
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Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.

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