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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-07-01
|
| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19636352/?tool=EBI |
| _version_ | 1818742506765942784 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T02:13:36Z |
| format | Article |
| id | doaj.art-7f49a632f6da494481e95c5bdce18ffe |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-18T02:13:36Z |
| publishDate | 2009-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-7f49a632f6da494481e95c5bdce18ffe2022-12-21T21:24:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852009-07-0177e100015910.1371/journal.pbio.1000159Natural killer cell signal integration balances synapse symmetry and migration.Fiona J CulleyMatthew JohnsonJ Henry EvansSunil KumarRupert CrillyJuan CasasbuenasTim SchnyderMaryam MehrabiMahendra P DeonarainDmitry S UshakovVeronique BraudGünter RothRoland BrockKarsten KöhlerDaniel M DavisNatural 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19636352/?tool=EBI |
| spellingShingle | 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. PLoS Biology |
| title | 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_short | Natural killer cell signal integration balances synapse symmetry and migration. |
| title_sort | natural killer cell signal integration balances synapse symmetry and migration |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19636352/?tool=EBI |
| work_keys_str_mv | AT fionajculley naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT matthewjohnson naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT jhenryevans naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT sunilkumar naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT rupertcrilly naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT juancasasbuenas naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT timschnyder naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT maryammehrabi naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT mahendrapdeonarain naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT dmitrysushakov naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT veroniquebraud naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT gunterroth naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT rolandbrock naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT karstenkohler naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration AT danielmdavis naturalkillercellsignalintegrationbalancessynapsesymmetryandmigration |