Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact

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 unde...

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Main Authors: Kumari, Sudha, Mak, Michael, Poh, Yeh Chuin, Tohme, Mira, Watson, Nicki, Melo, Mariane Bandeira, Janssen, Erin, Dustin, Michael, Geha, Raif, Irvine, Darrell J
Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering
Format: Article
Language:English
Published: EMBO 2020
Online Access:https://hdl.handle.net/1721.1/126042
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author Kumari, Sudha
Mak, Michael
Poh, Yeh Chuin
Tohme, Mira
Watson, Nicki
Melo, Mariane Bandeira
Janssen, Erin
Dustin, Michael
Geha, Raif
Irvine, Darrell J
author2 Massachusetts Institute of Technology. Department of Mechanical Engineering
author_facet Massachusetts Institute of Technology. Department of Mechanical Engineering
Kumari, Sudha
Mak, Michael
Poh, Yeh Chuin
Tohme, Mira
Watson, Nicki
Melo, Mariane Bandeira
Janssen, Erin
Dustin, Michael
Geha, Raif
Irvine, Darrell J
author_sort Kumari, Sudha
collection MIT
description 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.
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spelling mit-1721.1/1260422022-09-28T13:27:32Z Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact Kumari, Sudha Mak, Michael Poh, Yeh Chuin Tohme, Mira Watson, Nicki Melo, Mariane Bandeira Janssen, Erin Dustin, Michael Geha, Raif Irvine, Darrell J Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT 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. 2020-07-01T19:46:47Z 2020-07-01T19:46:47Z 2020-01 2019-11 2020-03-11T14:28:10Z Article http://purl.org/eprint/type/JournalArticle 0261-4189 1460-2075 https://hdl.handle.net/1721.1/126042 Kumari, Sudha et al. "Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact." EMBO Journal 39, 5 (January 2020): e102783 © 2020 The Authors en http://dx.doi.org/10.15252/embj.2019102783 EMBO Journal Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf EMBO EMBO Press
spellingShingle Kumari, Sudha
Mak, Michael
Poh, Yeh Chuin
Tohme, Mira
Watson, Nicki
Melo, Mariane Bandeira
Janssen, Erin
Dustin, Michael
Geha, Raif
Irvine, Darrell J
Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title_full Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title_fullStr Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title_full_unstemmed Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title_short Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
title_sort cytoskeletal tension actively sustains the migratory t cell synaptic contact
url https://hdl.handle.net/1721.1/126042
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