Natural killer cell signal integration balances synapse symmetry and migration.
Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question i...
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2009
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oai:doaj.org-article:7f49a632f6da494481e95c5bdce18ffe2021-11-25T05:34:05ZNatural killer cell signal integration balances synapse symmetry and migration.1544-91731545-788510.1371/journal.pbio.1000159https://doaj.org/article/7f49a632f6da494481e95c5bdce18ffe2009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19636352/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.Fiona J CulleyMatthew JohnsonJ Henry EvansSunil KumarRupert CrillyJuan CasasbuenasTim SchnyderMaryam MehrabiMahendra P DeonarainDmitry S UshakovVeronique BraudGünter RothRoland BrockKarsten KöhlerDaniel M DavisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 7, Iss 7, p e1000159 (2009) |
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Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Fiona J Culley Matthew Johnson J Henry Evans Sunil Kumar Rupert Crilly Juan Casasbuenas Tim Schnyder Maryam Mehrabi Mahendra P Deonarain Dmitry S Ushakov Veronique Braud Günter Roth Roland Brock Karsten Köhler Daniel M Davis Natural killer cell signal integration balances synapse symmetry and migration. |
| description |
Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response. |
| format |
article |
| author |
Fiona J Culley Matthew Johnson J Henry Evans Sunil Kumar Rupert Crilly Juan Casasbuenas Tim Schnyder Maryam Mehrabi Mahendra P Deonarain Dmitry S Ushakov Veronique Braud Günter Roth Roland Brock Karsten Köhler Daniel M Davis |
| author_facet |
Fiona J Culley Matthew Johnson J Henry Evans Sunil Kumar Rupert Crilly Juan Casasbuenas Tim Schnyder Maryam Mehrabi Mahendra P Deonarain Dmitry S Ushakov Veronique Braud Günter Roth Roland Brock Karsten Köhler Daniel M Davis |
| author_sort |
Fiona J Culley |
| title |
Natural killer cell signal integration balances synapse symmetry and migration. |
| title_short |
Natural killer cell signal integration balances synapse symmetry and migration. |
| title_full |
Natural killer cell signal integration balances synapse symmetry and migration. |
| title_fullStr |
Natural killer cell signal integration balances synapse symmetry and migration. |
| title_full_unstemmed |
Natural killer cell signal integration balances synapse symmetry and migration. |
| title_sort |
natural killer cell signal integration balances synapse symmetry and migration. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/7f49a632f6da494481e95c5bdce18ffe |
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