Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular proce...
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| Autor*in: |
Kumari, Sudha [verfasserIn] Mak, Michael [verfasserIn] Poh, Yeh‐Chuin [verfasserIn] Tohme, Mira [verfasserIn] Watson, Nicki [verfasserIn] Melo, Mariane [verfasserIn] Janssen, Erin [verfasserIn] Dustin, Michael [verfasserIn] Geha, Raif [verfasserIn] Irvine, Darrell J [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2020 |
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| Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 39(2020), 5 vom: 02. Jan. |
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| Übergeordnetes Werk: |
volume:39 ; year:2020 ; number:5 ; day:02 ; month:01 |
| Links: |
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| DOI / URN: |
10.15252/embj.2019102783 |
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| Katalog-ID: |
SPR058019278 |
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| 520 | |a Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. | ||
| 520 | |a Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. | ||
| 520 | |a Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. | ||
| 650 | 4 | |a actin cytoskeleton |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a immunological synapse |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a symmetry breaking |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a synapse mechanics |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a T‐cell migration |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Mak, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Poh, Yeh‐Chuin |e verfasserin |0 (orcid)0000-0003-3510-6369 |4 aut | |
| 700 | 1 | |a Tohme, Mira |e verfasserin |4 aut | |
| 700 | 1 | |a Watson, Nicki |e verfasserin |4 aut | |
| 700 | 1 | |a Melo, Mariane |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, Erin |e verfasserin |4 aut | |
| 700 | 1 | |a Dustin, Michael |e verfasserin |0 (orcid)0000-0003-4983-6389 |4 aut | |
| 700 | 1 | |a Geha, Raif |e verfasserin |4 aut | |
| 700 | 1 | |a Irvine, Darrell J |e verfasserin |0 (orcid)0000-0002-8637-1405 |4 aut | |
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10.15252/embj.2019102783 doi (DE-627)SPR058019278 (SPR)embj.2019102783-e DE-627 ger DE-627 rakwb eng Kumari, Sudha verfasserin (orcid)0000-0001-7082-2825 aut Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 Mak, Michael verfasserin aut Poh, Yeh‐Chuin verfasserin (orcid)0000-0003-3510-6369 aut Tohme, Mira verfasserin aut Watson, Nicki verfasserin aut Melo, Mariane verfasserin aut Janssen, Erin verfasserin aut Dustin, Michael verfasserin (orcid)0000-0003-4983-6389 aut Geha, Raif verfasserin aut Irvine, Darrell J verfasserin (orcid)0000-0002-8637-1405 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 39(2020), 5 vom: 02. Jan. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:39 year:2020 number:5 day:02 month:01 https://dx.doi.org/10.15252/embj.2019102783 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 39 2020 5 02 01 |
| spelling |
10.15252/embj.2019102783 doi (DE-627)SPR058019278 (SPR)embj.2019102783-e DE-627 ger DE-627 rakwb eng Kumari, Sudha verfasserin (orcid)0000-0001-7082-2825 aut Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 Mak, Michael verfasserin aut Poh, Yeh‐Chuin verfasserin (orcid)0000-0003-3510-6369 aut Tohme, Mira verfasserin aut Watson, Nicki verfasserin aut Melo, Mariane verfasserin aut Janssen, Erin verfasserin aut Dustin, Michael verfasserin (orcid)0000-0003-4983-6389 aut Geha, Raif verfasserin aut Irvine, Darrell J verfasserin (orcid)0000-0002-8637-1405 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 39(2020), 5 vom: 02. Jan. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:39 year:2020 number:5 day:02 month:01 https://dx.doi.org/10.15252/embj.2019102783 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 39 2020 5 02 01 |
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10.15252/embj.2019102783 doi (DE-627)SPR058019278 (SPR)embj.2019102783-e DE-627 ger DE-627 rakwb eng Kumari, Sudha verfasserin (orcid)0000-0001-7082-2825 aut Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 Mak, Michael verfasserin aut Poh, Yeh‐Chuin verfasserin (orcid)0000-0003-3510-6369 aut Tohme, Mira verfasserin aut Watson, Nicki verfasserin aut Melo, Mariane verfasserin aut Janssen, Erin verfasserin aut Dustin, Michael verfasserin (orcid)0000-0003-4983-6389 aut Geha, Raif verfasserin aut Irvine, Darrell J verfasserin (orcid)0000-0002-8637-1405 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 39(2020), 5 vom: 02. Jan. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:39 year:2020 number:5 day:02 month:01 https://dx.doi.org/10.15252/embj.2019102783 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 39 2020 5 02 01 |
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10.15252/embj.2019102783 doi (DE-627)SPR058019278 (SPR)embj.2019102783-e DE-627 ger DE-627 rakwb eng Kumari, Sudha verfasserin (orcid)0000-0001-7082-2825 aut Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 Mak, Michael verfasserin aut Poh, Yeh‐Chuin verfasserin (orcid)0000-0003-3510-6369 aut Tohme, Mira verfasserin aut Watson, Nicki verfasserin aut Melo, Mariane verfasserin aut Janssen, Erin verfasserin aut Dustin, Michael verfasserin (orcid)0000-0003-4983-6389 aut Geha, Raif verfasserin aut Irvine, Darrell J verfasserin (orcid)0000-0002-8637-1405 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 39(2020), 5 vom: 02. Jan. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:39 year:2020 number:5 day:02 month:01 https://dx.doi.org/10.15252/embj.2019102783 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 39 2020 5 02 01 |
| allfieldsSound |
10.15252/embj.2019102783 doi (DE-627)SPR058019278 (SPR)embj.2019102783-e DE-627 ger DE-627 rakwb eng Kumari, Sudha verfasserin (orcid)0000-0001-7082-2825 aut Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 Mak, Michael verfasserin aut Poh, Yeh‐Chuin verfasserin (orcid)0000-0003-3510-6369 aut Tohme, Mira verfasserin aut Watson, Nicki verfasserin aut Melo, Mariane verfasserin aut Janssen, Erin verfasserin aut Dustin, Michael verfasserin (orcid)0000-0003-4983-6389 aut Geha, Raif verfasserin aut Irvine, Darrell J verfasserin (orcid)0000-0002-8637-1405 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 39(2020), 5 vom: 02. Jan. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:39 year:2020 number:5 day:02 month:01 https://dx.doi.org/10.15252/embj.2019102783 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 39 2020 5 02 01 |
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Enthalten in The EMBO Journal 39(2020), 5 vom: 02. Jan. volume:39 year:2020 number:5 day:02 month:01 |
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Kumari, Sudha @@aut@@ Mak, Michael @@aut@@ Poh, Yeh‐Chuin @@aut@@ Tohme, Mira @@aut@@ Watson, Nicki @@aut@@ Melo, Mariane @@aut@@ Janssen, Erin @@aut@@ Dustin, Michael @@aut@@ Geha, Raif @@aut@@ Irvine, Darrell J @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR058019278</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20241024065151.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">241024s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.15252/embj.2019102783</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR058019278</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)embj.2019102783-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Kumari, Sudha</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-7082-2825</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2020</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">actin cytoskeleton</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">immunological synapse</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">symmetry breaking</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">synapse mechanics</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">T‐cell migration</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mak, Michael</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Poh, Yeh‐Chuin</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-3510-6369</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tohme, Mira</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Watson, Nicki</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Melo, Mariane</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Janssen, Erin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dustin, Michael</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-4983-6389</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Geha, Raif</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Irvine, Darrell J</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-8637-1405</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">The EMBO Journal</subfield><subfield code="d">Nature Publishing Group UK, 2023</subfield><subfield code="g">39(2020), 5 vom: 02. 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Kumari, Sudha |
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Kumari, Sudha misc actin cytoskeleton misc immunological synapse misc symmetry breaking misc synapse mechanics misc T‐cell migration Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact |
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Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact actin cytoskeleton (dpeaa)DE-He213 immunological synapse (dpeaa)DE-He213 symmetry breaking (dpeaa)DE-He213 synapse mechanics (dpeaa)DE-He213 T‐cell migration (dpeaa)DE-He213 |
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misc actin cytoskeleton misc immunological synapse misc symmetry breaking misc synapse mechanics misc T‐cell migration |
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Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact |
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Kumari, Sudha Mak, Michael Poh, Yeh‐Chuin Tohme, Mira Watson, Nicki Melo, Mariane Janssen, Erin Dustin, Michael Geha, Raif Irvine, Darrell J |
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Kumari, Sudha |
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cytoskeletal tension actively sustains the migratory t‐cell synaptic contact |
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Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact |
| abstract |
Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. © The Author(s) 2020 |
| abstractGer |
Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. © The Author(s) 2020 |
| abstract_unstemmed |
Abstract When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact. Synopsis When naïve T cells detect cognate antigens on the surface of antigen presenting cells, these highly migratory cells undergo immediate arrest and form radially symmetric cell‐cell conjugate interfaces termed immunological synapses. The stability of such synapses is a crucial determinant of T cell activation, but the T cell‐intrinsic mechanisms that regulate synaptic lifetime are not clear. This study finds that T cells construct specialized actin architectures within the immunological synapse to elevate cytoskeletal tension, thereby reinforcing synaptic stability. In T cells, lamellar protrusions would constantly attempt to break the synapse. Integrin activation is insufficient to sustain the synapse.Antigen recognition‐induced actin foci and associated actomyosin arrangements generate high in‐plane cytoskeletal tension that actively restrains synapse breaking.Via nucleation of actin foci, WASP acts as a central regulator of this mechanism. Downregulation of WASP following T cell activation leads to loss of foci‐dependent actin architecture resulting into synapse unravelling.T cells that lack WASP are predisposed to synapse symmetry breaking, irrespective of the substrate stiffness. Graphical Abstract The stability of contact sites between T‐cells and antigen‐presenting cells—the immunological synapse– is regulated by WASP‐mediated nucleation of F‐actin foci and the actomyosin network, generating cytoskeletal tension that prevents synapse breaking. © The Author(s) 2020 |
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| score |
7.4017944 |