NK Cell Lytic Granules Are Highly Motile at the Immunological Synapse and Require F-Actin for Post-Degranulation Persistence

Mace, Emily M.; Wu, Winona; Ho, Tina; Mann, Shaina S; Hsu, Hui‐Chen; Orange, Jordan S.

doi:10.4049/jimmunol.1201296

Cited by 33 publications

(37 citation statements)

References 27 publications

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“…92, 122 This movement is not dependent upon F-actin dynamic rearrangement, 122 but a role for microtubule dynamics has not been excluded. Granule movement may be undirected rolling on synaptic actin, seeking regions of hypodensity.…”

Section: Stages Of Lytic Synapse Formationmentioning

confidence: 99%

Cell biological steps and checkpoints in accessing NK cell cytotoxicity

et al. 2014

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Natural killer (NK) cell-mediated cytotoxicity is governed by the formation of a lytic immune synapse in discrete regulated steps, which give rise to an extensive array of cellular checkpoints in accessing NK cell-mediated cytolytic defense. Appropriate progression through these cell biological steps is critical for the directed secretion of specialized secretory lysosomes and subsequent target cell death. Here we highlight recent discoveries in the formation of the NK cell cytolytic synapse as well as the molecular steps and cell biological checkpoints required for this essential host defense process.

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Section: Stages Of Lytic Synapse Formationmentioning

confidence: 99%

Cell biological steps and checkpoints in accessing NK cell cytotoxicity

et al. 2014

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“…These have distinct patterns of movement, as classified by highly quantitative and unbiased analysis of a large number of lytic granules by TIRFm and particle tracking (Liu et al, 2010). This granule dynamism is also seen in activated cells, prior to but not following granule exocytosis using similarly quantitative and unbiased analyses (Mace et al, 2012). Neither the function nor the mechanism of such extensive granule movement at the cortex is completely understood.…”

Section: Lytic Granule Behavior Determined By Total Internal Reflectimentioning

confidence: 85%

“…In particular, the visualization of degranulation has been aided by pHlourin, a pH sensitive variant of GFP that does not fluoresce at the acidic pH found in lytic granules, but upon exposure to neutral pH after degranulation fluoresces green (Miesenbock et al, 1998). By fusing pHluorin to the lumenal portion of granules using LAMP-1 or FasL, both of which sort to lytic granules (Peters et al, 1991; Bossi and Griffiths, 1999), individual degranulation events can be tracked by TIRF (Liu et al, 2011; Rak et al, 2011; Mace et al, 2012) or even by confocal of NK cells in conjugates (Mace et al, 2012). …”

Section: Lytic Granule Behavior Determined By Total Internal Reflectimentioning

confidence: 99%

New views of the human NK cell immunological synapse: recent advances enabled by super- and high-resolution imaging techniques

Mace¹

2013

Front. Immun.

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Imaging technology has undergone rapid growth with the development of super resolution microscopy, which enables resolution below the diffraction barrier of light (~200 nm). In addition, new techniques for single molecule imaging are being added to the cell biologist’s arsenal. Immunologists have exploited these techniques to advance understanding of NK biology, particularly that of the immune synapse. The immune synapse’s relatively small size and complex architecture combined with its exquisitely controlled signaling milieu have made it a challenge to visualize. In this review we highlight and discuss new insights into NK cell immune synapse formation and regulation revealed by cutting edge imaging techniques, including super-resolution microscopy, high-resolution total internal reflection microscopy, and Förster resonance energy transfer.

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“…Actin, which is considered a marker for the early IS, was recently shown by TIRFM to also play a role in LG degranulation itself (33). …”

Section: Visualizing and Quantifying Lytic Granules At The Is By Tirfmmentioning

confidence: 99%

In the Crosshairs: Investigating Lytic Granules by High-Resolution Microscopy and Electrophysiology

et al. 2013

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Cytotoxic T lymphocytes (CTLs) form an integral part of the adaptive immune system. Their main function is to eliminate bacteria- and virus-infected target cells by releasing perforin and granzymes (the lethal hit) contained within lytic granules (LGs), at the CTL-target-cell interface [the immunological synapse (IS)]. The formation of the IS as well as the final events at the IS leading to target-cell death are both highly complex and dynamic processes. In this review we highlight and discuss three high-resolution techniques that have proven invaluable in the effort to decipher key features of the mechanism of CTL effector function and in particular lytic granule maturation and fusion. Correlative light and electron microscopy allows the correlation between organelle morphology and localization of particular proteins, while total internal reflection fluorescence microscopy (TIRFM) enables the study of lytic granule dynamics at the IS in real time. The combination of TIRFM with patch-clamp membrane capacitance measurements finally provides a tool to quantify the size of fusing LGs at the IS.

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NK Cell Lytic Granules Are Highly Motile at the Immunological Synapse and Require F-Actin for Post-Degranulation Persistence

Cited by 33 publications

References 27 publications

Cell biological steps and checkpoints in accessing NK cell cytotoxicity

Cell biological steps and checkpoints in accessing NK cell cytotoxicity

New views of the human NK cell immunological synapse: recent advances enabled by super- and high-resolution imaging techniques

In the Crosshairs: Investigating Lytic Granules by High-Resolution Microscopy and Electrophysiology

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