Compositional Characterization of the Cytoskeleton of NK-Like Cells

Meng, Xu; Wilkins, John A.

doi:10.1021/pr0502121

Cited by 22 publications

(34 citation statements)

References 24 publications

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“…Our previous proteomic analysis of YTS cells identified PPP1R9B as a component of their cytoskeleton [16]. As PPP1R9B has been shown to regulate actin deposition and neurite formation, we questioned whether PPP1R9B might also be involved in immunological synapse formation [19].…”

Section: Ppp1r9b Accumulates At the Nkis And Sites Of Homotypic Cell mentioning

confidence: 97%

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PPP1R9B (Neurabin 2): Involvement and dynamics in the NK immunological synapse

Meng

Kanwar

et al. 2009

Eur J Immunol

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The NK immunological synapse (NKIS) is a dynamic structure dependent on the assembly of membrane, cytoskeletal and signaling components. These serve to focus and generate stimuli for adhesion and orientation of the cytoskeleton for targeted cytolytic granule release. Previous studies have demonstrated the importance of the cytoskeleton in these processes. We previously identified PPP1R9B (neurabin 2, spinophilin) as a cytoskeletal component of the NK-like cell line YTS. We demonstrate that (i) PPP1R9B gradually accumulates at the NKIS in a maturation stage-dependent manner; (ii) it mimics the early kinetics of actin recruitment to the NKIS but it precedes actin departure from the site; (iii) it is recruited by CD18 stimulation but not by CD28 ligation; (iv) it is required for the maintenance of the cortical F-actin organization in the YTS cells and knocking down PPP1R9B reduces the frequency of YTS-target cell conjugation, possibly due to the collapsed F-actin cytoskeleton in these cells. These results indicate that PPP1R9B is required for synapse formation in the NK cells and suggest that it may be involved in the maintenance of cellular architecture by regulation of actin assembly, possibly acting to stabilize the NKIS until granule release is eminent.Key words: CD18 . CD28 . NK . PPP1R9B . Synapse IntroductionThe immunological synapse is central to immune recognition and activation [1,2]. In cytotoxic cells such as NK cells, the synapse plays an additional role of focusing the effector-phase response onto the conjugated target cell [3,4]. This serves to minimize the potential for ''off target'' cytotoxic effects on bystander cells.The NK immunological synapse (NKIS) develops as an initial stimulatory complex with an integrated fail-safe mechanism, which allows for inhibition of responses by inhibitory receptors that prevent activation by inappropriate targets [5][6][7][8]. In productive NKIS formation, there is a rapid sequence of events that transition from contact to activation, granule polarization and release with subsequent abandonment of the damaged target cell. These events are dependent upon a carefully orchestrated series of molecular events that require cytoskeletal assembly and translocation of cytolytic granules to the immune synapse where membrane fusion and granule content release occurs [9].The cytoskeleton plays an essential role in all aspects of these processes as interference with microtubule or microfilament functions assembly inhibits NKIS formation and function [10]. It is also apparent that the actin cytoskeleton is in a dynamic state undergoing rearrangement at the synapse to allow granule access and fusion with the effector plasma membrane [3,11,12]. This Ã These authors contributed equally to this work. 552requires localized alterations in F-actin organization through modulations in bundling and scaffolding molecules [13][14][15]. Despite the appreciation of the importance of these processes, there is still rather limited information regarding the composition and functionality of th...

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Section: Ppp1r9b Accumulates At the Nkis And Sites Of Homotypic Cell mentioning

confidence: 97%

“…In a previous study, we identified a number of cytoskeletal components of the NK-cell line, YTS [16]. Potential candidates of NKIS proteins were selected for analysis based on their predicted or known roles in cell polarization in other cell types.…”

Section: Introductionmentioning

confidence: 99%

PPP1R9B (Neurabin 2): Involvement and dynamics in the NK immunological synapse

Meng

Kanwar

et al. 2009

Eur J Immunol

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“…IQGAP has been detected in NK cells [24] and YTS cells [12]. However, it is unclear as to what roles it plays in cell-mediated effector processes.…”

Section: Effects Of Iqgap1 Silencing On Yts Cellsmentioning

confidence: 99%

“…41: 2763-2773 DOI 10.1002 Molecular immunology 2763 determined, in part because of the difficulties associated with the isolation of these structures. In an effort to define the NKIS composition, we previously performed a proteomic analysis of the cytoskeletal elements of an NK-like cell line YTS, with subsequent structural and bioinformatic approaches to identify candidate synapse components [12]. IQGAP1was identified as one of the cytoskeletal components of the YTS cells [12].…”

Section: Introductionmentioning

confidence: 99%

“…In an effort to define the NKIS composition, we previously performed a proteomic analysis of the cytoskeletal elements of an NK-like cell line YTS, with subsequent structural and bioinformatic approaches to identify candidate synapse components [12]. IQGAP1was identified as one of the cytoskeletal components of the YTS cells [12]. It is a large multi-domain protein with the capacity to interact with a wide range of molecular species including Rac1 and Cdc42.…”

Section: Introductionmentioning

confidence: 99%

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IQGAP1 involvement in MTOC and granule polarization in NK‐cell cytotoxicity

Kanwar

Wilkins

2011

Eur J Immunol

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Natural killer (NK) cells form a region of tight contact called the NK immunological synapse (NKIS) with their target cells. This is a dynamic region serving as a platform for targeted signaling and exocytotic events. We previously identified IQGAP1 as a cytoskeletal component of the NK-like cell line YTS. The present study was undertaken to determine the role of IQGAP1 in the function of NK cells. Silencing of IQGAP1 expression resulted in almost complete loss of the cytotoxic activity of YTS cells. Loss of IQGAP1 did not prevent conjugate formation with target cells but it did result in a failure to reorient the microtubule organizing centre to the immune synapse. Significantly, IQGAP1 expression was required for the perigranular accumulation of an F-actin network. IQGAP1 was shown to undergo marked rearrangements during synapse maturation in effector target conjugates of YTS or primary NK cells. These results suggest previously undescribed role(s) for IQGAP1 in regulating multiple aspects of cytoskeletal organization and granule polarization in NK cells.Key words: Immune synapse . IQGAP1 . MTOC . NK cells . shRNA Supporting Information available online IntroductionNatural killer (NK) cells are lymphocytes of the innate immune system that eliminate allogeneic cells and cells undergoing physiological stress due to viral, bacterial, or parasitic infection or malignant transformation [1][2][3][4][5]. NK cells form an immunological synapse (NKIS) that serves to tether them to target cells and provide a site for the targeted delivery of lytic granules [6,7]. In order to achieve this, a series of coordinated surface and intracellular molecular changes must occur within the NK cells [8]. These include the polarization and patterning of surface proteins, formation of a submembranous actin matrix, and the reorientation of the microtubule organizing centre (MTOC) for the delivery and fusion of granules with the effector membrane. Once some of the granules have fused with the plasma membrane, the NK cells disengage from their targets to repeat this process with other target cells.These processes of target cell engagement and degranulation are carefully regulated involving a coordinated sequence of events. These include extensive reorganization of NKIS surface elements to form specialized regions for membrane granule fusion [9]. Concurrently, the actin and tubulin cytoskeleton and associated molecules reorganize to allow granules access to the membrane [10,11]. While many of the membrane proximal events involved in NKIS formation have been characterized, the composition of the more distal NKIS elements has not been fully Eur. J. Immunol. 2011. 41: 2763-2773 DOI 10.1002 Molecular immunology 2763 determined, in part because of the difficulties associated with the isolation of these structures. In an effort to define the NKIS composition, we previously performed a proteomic analysis of the cytoskeletal elements of an NK-like cell line YTS, with subsequent structural and bioinformatic approaches to identify candidate synapse...

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Swiprosin‐1: Its Expression and Diverse Biological Functions

Thylur

Gowda

Mishra

et al. 2017

J of Cellular Biochemistry

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Swiprosin-1/EFhd2 is a Ca 2þ binding adapter protein involved in the various cellular functions. Swiprosin-1 is significantly upregulated in a number of pathological conditions of inflammation, neurodegeneration, and cancer. Swiprosin-1 associated with actin and its expression level amplifies the production of proinflammatory mediators and modulates the activation of transcription factor during immune cells activation. This review aims at providing an overview of the expression and function of swiprosin-1/EFhd2 in various pathophysiological conditions. We also discussed the key role of swiprosin-1 in immune cell activation, cell migration, apoptosis, humoral immunity, cancer invasion and metastasis, neuronal transport, and major signaling cascades. J. Cell. Biochem. 119: 150-156, 2018.

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Compositional Characterization of the Cytoskeleton of NK-Like Cells

Cited by 22 publications

References 24 publications

PPP1R9B (Neurabin 2): Involvement and dynamics in the NK immunological synapse

PPP1R9B (Neurabin 2): Involvement and dynamics in the NK immunological synapse

IQGAP1 involvement in MTOC and granule polarization in NK‐cell cytotoxicity

Swiprosin‐1: Its Expression and Diverse Biological Functions

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