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ADP-ribose/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells

Natural killer (NK) cells are essential for immunosurveillance against transformed cells. Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel gated by ADP-ribose (ADPR). However, the role of TRPM2-mediated Ca(2+) signaling in the antitumor response of NK cells has... Full description

Journal Title: Scientific reports 25 March 2015, Vol.5, pp.9482
Main Author: Rah, So-Young
Other Authors: Kwak, Jae-Yong , Chung, Yun-Jo , Kim, Uh-Hyun
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 2045-2322 ; PMID: 25879940 Version:1 ; DOI: 10.1038/srep09482
Link: http://pubmed.gov/25879940
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title: ADP-ribose/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells
format: Article
creator:
  • Rah, So-Young
  • Kwak, Jae-Yong
  • Chung, Yun-Jo
  • Kim, Uh-Hyun
subjects:
  • Calcium Signaling
  • Adenosine Diphosphate Ribose -- Metabolism
  • Killer Cells, Natural -- Immunology
  • Trpm Cation Channels -- Metabolism
ispartof: Scientific reports, 25 March 2015, Vol.5, pp.9482
description: Natural killer (NK) cells are essential for immunosurveillance against transformed cells. Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel gated by ADP-ribose (ADPR). However, the role of TRPM2-mediated Ca(2+) signaling in the antitumor response of NK cells has not been explored. Here, we show that ADPR-mediated Ca(2+) signaling is important for cytolytic granule polarization and degranulation but not involved in target cell recognition by NK cells. The key steps of this pathway are: 1) the activation of intracellular CD38 by protein kinase A following the interaction of the NK cell with a tumor cell results in the production of ADPR, 2) ADPR targets TRPM2 channels on cytolytic granules, and 3) TRPM2-mediated Ca(2+) signaling induces cytolytic granule polarization and degranulation, resulting in antitumor activity. NK cells treated with 8-Br-ADPR, an ADPR antagonist, as well as NK cells from Cd38(-/-) mice showed reduced tumor-induced granule polarization,...
language: eng
source:
identifier: E-ISSN: 2045-2322 ; PMID: 25879940 Version:1 ; DOI: 10.1038/srep09482
fulltext: fulltext
issn:
  • 20452322
  • 2045-2322
url: Link


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titleADP-ribose/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells
creatorRah, So-Young ; Kwak, Jae-Yong ; Chung, Yun-Jo ; Kim, Uh-Hyun
ispartofScientific reports, 25 March 2015, Vol.5, pp.9482
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subjectCalcium Signaling ; Adenosine Diphosphate Ribose -- Metabolism ; Killer Cells, Natural -- Immunology ; Trpm Cation Channels -- Metabolism
descriptionNatural killer (NK) cells are essential for immunosurveillance against transformed cells. Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel gated by ADP-ribose (ADPR). However, the role of TRPM2-mediated Ca(2+) signaling in the antitumor response of NK cells has not been explored. Here, we show that ADPR-mediated Ca(2+) signaling is important for cytolytic granule polarization and degranulation but not involved in target cell recognition by NK cells. The key steps of this pathway are: 1) the activation of intracellular CD38 by protein kinase A following the interaction of the NK cell with a tumor cell results in the production of ADPR, 2) ADPR targets TRPM2 channels on cytolytic granules, and 3) TRPM2-mediated Ca(2+) signaling induces cytolytic granule polarization and degranulation, resulting in antitumor activity. NK cells treated with 8-Br-ADPR, an ADPR antagonist, as well as NK cells from Cd38(-/-) mice showed reduced tumor-induced granule polarization,...
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descriptionNatural killer (NK) cells are essential for immunosurveillance against transformed cells. Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel gated by ADP-ribose (ADPR). However, the role of TRPM2-mediated Ca(2+) signaling in the antitumor response of NK cells has not been explored. Here, we show that ADPR-mediated Ca(2+) signaling is important for cytolytic granule polarization and degranulation but not involved in target cell recognition by NK cells. The key steps of this pathway are: 1) the activation of intracellular CD38 by protein kinase A following the interaction of the NK cell with a tumor cell results in the production of ADPR, 2) ADPR targets TRPM2 channels on cytolytic granules, and 3) TRPM2-mediated Ca(2+) signaling induces cytolytic granule polarization and degranulation, resulting in antitumor activity. NK cells treated with 8-Br-ADPR, an ADPR antagonist, as well as NK cells from Cd38(-/-) mice showed reduced tumor-induced granule polarization,...
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abstractNatural killer (NK) cells are essential for immunosurveillance against transformed cells. Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel gated by ADP-ribose (ADPR). However, the role of TRPM2-mediated Ca(2+) signaling in the antitumor response of NK cells has not been explored. Here, we show that ADPR-mediated Ca(2+) signaling is important for cytolytic granule polarization and degranulation but not involved in target cell recognition by NK cells. The key steps of this pathway are: 1) the activation of intracellular CD38 by protein kinase A following the interaction of the NK cell with a tumor cell results in the production of ADPR, 2) ADPR targets TRPM2 channels on cytolytic granules, and 3) TRPM2-mediated Ca(2+) signaling induces cytolytic granule polarization and degranulation, resulting in antitumor activity. NK cells treated with 8-Br-ADPR, an ADPR antagonist, as well as NK cells from Cd38(-/-) mice showed reduced tumor-induced granule polarization,...
doi10.1038/srep09482
pmid25879940
issue1
date2015-03-25