Cargando…
Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity
Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known as lytic granules, which upon formation of immune synapse with the target cell, polarize toward the immune synapse to deliver their contents to the target cell membrane. Here, we identify a small GTP-binding protein, A...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842998/ https://www.ncbi.nlm.nih.gov/pubmed/24088571 http://dx.doi.org/10.1091/mbc.E13-05-0259 |
_version_ | 1782293025003667456 |
---|---|
author | Tuli, Amit Thiery, Jerome James, Ashley M. Michelet, Xavier Sharma, Mahak Garg, Salil Sanborn, Keri B. Orange, Jordan S. Lieberman, Judy Brenner, Michael B. |
author_facet | Tuli, Amit Thiery, Jerome James, Ashley M. Michelet, Xavier Sharma, Mahak Garg, Salil Sanborn, Keri B. Orange, Jordan S. Lieberman, Judy Brenner, Michael B. |
author_sort | Tuli, Amit |
collection | PubMed |
description | Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known as lytic granules, which upon formation of immune synapse with the target cell, polarize toward the immune synapse to deliver their contents to the target cell membrane. Here, we identify a small GTP-binding protein, ADP-ribosylation factor-like 8b (Arl8b), as a critical factor required for NK cell–mediated cytotoxicity. Our findings indicate that Arl8b drives the polarization of lytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. Using a glutathione S-transferase pull-down approach, we identify kinesin family member 5B (KIF5B; the heavy chain of kinesin-1) as an interaction partner of Arl8b from NK cell lysates. Previous studies showed that interaction between kinesin-1 and Arl8b is mediated by SifA and kinesin-interacting protein (SKIP) and the tripartite complex drives the anterograde movement of lysosomes. Silencing of both KIF5B and SKIP in NK cells, similar to Arl8b, led to failure of MTOC-lytic granule polarization to the immune synapse, suggesting that Arl8b and kinesin-1 together control this critical step in NK cell cytotoxicity. |
format | Online Article Text |
id | pubmed-3842998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38429982014-02-16 Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity Tuli, Amit Thiery, Jerome James, Ashley M. Michelet, Xavier Sharma, Mahak Garg, Salil Sanborn, Keri B. Orange, Jordan S. Lieberman, Judy Brenner, Michael B. Mol Biol Cell Articles Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known as lytic granules, which upon formation of immune synapse with the target cell, polarize toward the immune synapse to deliver their contents to the target cell membrane. Here, we identify a small GTP-binding protein, ADP-ribosylation factor-like 8b (Arl8b), as a critical factor required for NK cell–mediated cytotoxicity. Our findings indicate that Arl8b drives the polarization of lytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. Using a glutathione S-transferase pull-down approach, we identify kinesin family member 5B (KIF5B; the heavy chain of kinesin-1) as an interaction partner of Arl8b from NK cell lysates. Previous studies showed that interaction between kinesin-1 and Arl8b is mediated by SifA and kinesin-interacting protein (SKIP) and the tripartite complex drives the anterograde movement of lysosomes. Silencing of both KIF5B and SKIP in NK cells, similar to Arl8b, led to failure of MTOC-lytic granule polarization to the immune synapse, suggesting that Arl8b and kinesin-1 together control this critical step in NK cell cytotoxicity. The American Society for Cell Biology 2013-12-01 /pmc/articles/PMC3842998/ /pubmed/24088571 http://dx.doi.org/10.1091/mbc.E13-05-0259 Text en © 2013 Tuli et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Tuli, Amit Thiery, Jerome James, Ashley M. Michelet, Xavier Sharma, Mahak Garg, Salil Sanborn, Keri B. Orange, Jordan S. Lieberman, Judy Brenner, Michael B. Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title | Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title_full | Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title_fullStr | Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title_full_unstemmed | Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title_short | Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
title_sort | arf-like gtpase arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842998/ https://www.ncbi.nlm.nih.gov/pubmed/24088571 http://dx.doi.org/10.1091/mbc.E13-05-0259 |
work_keys_str_mv | AT tuliamit arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT thieryjerome arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT jamesashleym arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT micheletxavier arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT sharmamahak arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT gargsalil arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT sanbornkerib arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT orangejordans arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT liebermanjudy arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity AT brennermichaelb arflikegtpasearl8bregulateslyticgranulepolarizationandnaturalkillercellmediatedcytotoxicity |