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T cell responses to antigen are initiated by engagement of the T cell receptor (TCR)1, leading to activation of diverse signaling cascades, including an incompletely defined pathway that triggers rapid remodeling of the actin cytoskeleton. Defects in the control of actin dynamics and organization are associated with several human immunodeficiency diseases, emphasizing the importance of cytoskeletal remodeling in the functioning of the adaptive immune system. Here, we investigate the role of the adaptor protein Bcl102 in the control of actin dynamics. Although Bcl10 is primarily known as a component of the pathway connecting the TCR to activation of the NF-κB3 transcription factor, a few studies have implicated Bcl10 in antigen receptor-dependent control of actin polymerization and F-actin-dependent functional responses. However, the role of Bcl10 in the regulation of cytoskeletal dynamics remains largely undefined. To investigate the contribution of Bcl10 in the regulation of TCR-dependent cytoskeletal dynamics, we monitored actin dynamics at the immune synapse of primary murine CD8 effector T cells. Quantification of these dynamics reveals two distinct temporal phases distinguished by differences in speed and directionality. Our results indicate that effector CD8 T cells lacking Bcl10 display faster actin flows and more dynamic lamellipodia, compared to wild-type cells. These studies define a role for Bcl10 in TCR-dependent actin dynamics, emphasizing that Bcl10 has important cytoskeleton-directed functions that are likely independent of its role in transmission of NF-κB -activating signals. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Kaustubh Wagh, Brittany A Wheatley, Maria K Traver, Imran Hussain, Brian C Schaefer, Arpita Upadhyaya. Bcl10 is associated with actin dynamics at the T cell immune synapse. Cellular immunology. 2020 Oct;356:104161

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PMID: 32768663

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