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PLoS One. 2015 Aug 3;10(8):e0133231. doi: 10.1371/journal.pone.0133231. eCollection 2015.

Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling.

Author information

1
Department of Immunology, UT Southwestern Medical Center, Dallas, Texas, United States of America.
2
Children's Hospital of Philadelphia Abramson Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
3
School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
4
School of Biochemistry, University of Bristol, Bristol, United Kingdom.
5
Department of Immunology, UT Southwestern Medical Center, Dallas, Texas, United States of America; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, United States of America.

Abstract

Dynamic subcellular distributions of signaling system components are critical regulators of cellular signal transduction through their control of molecular interactions. Understanding how signaling activity depends on such distributions and the cellular structures driving them is required for comprehensive insight into signal transduction. In the activation of primary murine T cells by antigen presenting cells (APC) signaling intermediates associate with various subcellular structures, prominently a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell. While actin dynamics are well established as general regulators of cellular organization, their role in controlling signaling organization in primary T cell:APC couples and the specific cellular structures driving it is unresolved. Using modest interference with actin dynamics with a low concentration of Jasplakinolide as corroborated by costimulation blockade we show that T cell actin preferentially controls lamellal signaling localization and activity leading downstream to calcium signaling. Lamellal localization repeatedly related to efficient T cell function. This suggests that the transient lamellal actin matrix regulates T cell signaling associations that facilitate T cell activation.

PMID:
26237588
PMCID:
PMC4523178
DOI:
10.1371/journal.pone.0133231
[Indexed for MEDLINE]
Free PMC Article

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