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Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse

Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, l...

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Autores principales: Murugesan, Sricharan, Hong, Jinsung, Yi, Jason, Li, Dong, Beach, Jordan R., Shao, Lin, Meinhardt, John, Madison, Grey, Wu, Xufeng, Betzig, Eric, Hammer, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100289/
https://www.ncbi.nlm.nih.gov/pubmed/27799367
http://dx.doi.org/10.1083/jcb.201603080
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author Murugesan, Sricharan
Hong, Jinsung
Yi, Jason
Li, Dong
Beach, Jordan R.
Shao, Lin
Meinhardt, John
Madison, Grey
Wu, Xufeng
Betzig, Eric
Hammer, John A.
author_facet Murugesan, Sricharan
Hong, Jinsung
Yi, Jason
Li, Dong
Beach, Jordan R.
Shao, Lin
Meinhardt, John
Madison, Grey
Wu, Xufeng
Betzig, Eric
Hammer, John A.
author_sort Murugesan, Sricharan
collection PubMed
description Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs. Three-dimensional SIM shows that active LFA-1 often aligns with arcs, whereas TCR MCs commonly reside between arcs, and total internal reflection fluorescence SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, missegregated integrin clusters, decreased T–B cell adhesion, and diminished TCR signaling. Together, our results define the origin, organization, and functional significance of a major actomyosin contractile structure at the IS that directly propels TCR MC transport.
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spelling pubmed-51002892017-05-07 Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse Murugesan, Sricharan Hong, Jinsung Yi, Jason Li, Dong Beach, Jordan R. Shao, Lin Meinhardt, John Madison, Grey Wu, Xufeng Betzig, Eric Hammer, John A. J Cell Biol Research Articles Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs. Three-dimensional SIM shows that active LFA-1 often aligns with arcs, whereas TCR MCs commonly reside between arcs, and total internal reflection fluorescence SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, missegregated integrin clusters, decreased T–B cell adhesion, and diminished TCR signaling. Together, our results define the origin, organization, and functional significance of a major actomyosin contractile structure at the IS that directly propels TCR MC transport. The Rockefeller University Press 2016-11-07 /pmc/articles/PMC5100289/ /pubmed/27799367 http://dx.doi.org/10.1083/jcb.201603080 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Murugesan, Sricharan
Hong, Jinsung
Yi, Jason
Li, Dong
Beach, Jordan R.
Shao, Lin
Meinhardt, John
Madison, Grey
Wu, Xufeng
Betzig, Eric
Hammer, John A.
Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title_full Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title_fullStr Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title_full_unstemmed Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title_short Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse
title_sort formin-generated actomyosin arcs propel t cell receptor microcluster movement at the immune synapse
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100289/
https://www.ncbi.nlm.nih.gov/pubmed/27799367
http://dx.doi.org/10.1083/jcb.201603080
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