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The actin-driven spatiotemporal organization of T-cell signaling at the system scale

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The actin-driven spatiotemporal organization of T-cell signaling at the system scale. / Roybal, Kole T; Sinai, Parisa; Verkade, Paul; Murphy, Robert; Wülfing, Christoph.

In: Immunological Reviews, Vol. 256, No. 1, 11.2013, p. 133-147.

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Roybal, Kole T ; Sinai, Parisa ; Verkade, Paul ; Murphy, Robert ; Wülfing, Christoph. / The actin-driven spatiotemporal organization of T-cell signaling at the system scale. In: Immunological Reviews. 2013 ; Vol. 256, No. 1. pp. 133-147.

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@article{256fa235318f48fab2b5749210bd1ee0,
title = "The actin-driven spatiotemporal organization of T-cell signaling at the system scale",
abstract = "T cells are activated through interaction with antigen-presenting cells (APCs). During activation, receptors and signaling intermediates accumulate in diverse spatiotemporal distributions. These distributions control the probability of signaling interactions and thus govern information flow through the signaling system. Spatiotemporally resolved system-scale investigation of signaling can extract the regulatory information thus encoded, allowing unique insight into the control of T-cell function. Substantial technical challenges exist, and these are briefly discussed herein. While much of the work assessing T-cell spatiotemporal organization uses planar APC substitutes, we focus here on B-cell APCs with often stark differences. Spatiotemporal signaling distributions are driven by cell biologically distinct structures, a large protein assembly at the interface center, a large invagination, the actin-supported interface periphery as extended by smaller individual lamella, and a newly discovered whole-interface actin-driven lamellum. The more than 60 elements of T-cell activation studied to date are dynamically distributed between these structures, generating a complex organization of the signaling system. Signal initiation and core signaling prefer the interface center, while signal amplification is localized in the transient lamellum. Actin dynamics control signaling distributions through regulation of the underlying structures and drive a highly undulating T-cell/APC interface that imposes substantial constraints on T-cell organization. We suggest that the regulation of actin dynamics, by controlling signaling distributions and membrane topology, is an important rheostat of T-cell signaling.",
keywords = "Actins, Animals, Antigen-Presenting Cells, Cell Communication, Humans, Lymphocyte Activation, Signal Transduction, T-Lymphocytes, T-cell signaling, Systems biology, Imaging, Actin",
author = "Roybal, {Kole T} and Parisa Sinai and Paul Verkade and Robert Murphy and Christoph W{\"u}lfing",
year = "2013",
month = "11",
doi = "10.1111/imr.12103",
language = "English",
volume = "256",
pages = "133--147",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - The actin-driven spatiotemporal organization of T-cell signaling at the system scale

AU - Roybal, Kole T

AU - Sinai, Parisa

AU - Verkade, Paul

AU - Murphy, Robert

AU - Wülfing, Christoph

PY - 2013/11

Y1 - 2013/11

N2 - T cells are activated through interaction with antigen-presenting cells (APCs). During activation, receptors and signaling intermediates accumulate in diverse spatiotemporal distributions. These distributions control the probability of signaling interactions and thus govern information flow through the signaling system. Spatiotemporally resolved system-scale investigation of signaling can extract the regulatory information thus encoded, allowing unique insight into the control of T-cell function. Substantial technical challenges exist, and these are briefly discussed herein. While much of the work assessing T-cell spatiotemporal organization uses planar APC substitutes, we focus here on B-cell APCs with often stark differences. Spatiotemporal signaling distributions are driven by cell biologically distinct structures, a large protein assembly at the interface center, a large invagination, the actin-supported interface periphery as extended by smaller individual lamella, and a newly discovered whole-interface actin-driven lamellum. The more than 60 elements of T-cell activation studied to date are dynamically distributed between these structures, generating a complex organization of the signaling system. Signal initiation and core signaling prefer the interface center, while signal amplification is localized in the transient lamellum. Actin dynamics control signaling distributions through regulation of the underlying structures and drive a highly undulating T-cell/APC interface that imposes substantial constraints on T-cell organization. We suggest that the regulation of actin dynamics, by controlling signaling distributions and membrane topology, is an important rheostat of T-cell signaling.

AB - T cells are activated through interaction with antigen-presenting cells (APCs). During activation, receptors and signaling intermediates accumulate in diverse spatiotemporal distributions. These distributions control the probability of signaling interactions and thus govern information flow through the signaling system. Spatiotemporally resolved system-scale investigation of signaling can extract the regulatory information thus encoded, allowing unique insight into the control of T-cell function. Substantial technical challenges exist, and these are briefly discussed herein. While much of the work assessing T-cell spatiotemporal organization uses planar APC substitutes, we focus here on B-cell APCs with often stark differences. Spatiotemporal signaling distributions are driven by cell biologically distinct structures, a large protein assembly at the interface center, a large invagination, the actin-supported interface periphery as extended by smaller individual lamella, and a newly discovered whole-interface actin-driven lamellum. The more than 60 elements of T-cell activation studied to date are dynamically distributed between these structures, generating a complex organization of the signaling system. Signal initiation and core signaling prefer the interface center, while signal amplification is localized in the transient lamellum. Actin dynamics control signaling distributions through regulation of the underlying structures and drive a highly undulating T-cell/APC interface that imposes substantial constraints on T-cell organization. We suggest that the regulation of actin dynamics, by controlling signaling distributions and membrane topology, is an important rheostat of T-cell signaling.

KW - Actins

KW - Animals

KW - Antigen-Presenting Cells

KW - Cell Communication

KW - Humans

KW - Lymphocyte Activation

KW - Signal Transduction

KW - T-Lymphocytes

KW - T-cell signaling

KW - Systems biology

KW - Imaging

KW - Actin

U2 - 10.1111/imr.12103

DO - 10.1111/imr.12103

M3 - Article

VL - 256

SP - 133

EP - 147

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

IS - 1

ER -