Action and Traction: Cytoskeletal Control of Receptor Triggering at the Immunological Synapse

被引:84
作者
Comrie, William A. [1 ,2 ]
Burkhardt, Janis K. [1 ]
机构
[1] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
关键词
immunological synapse; actin; cytoskeleton; mechanotransduction; integrin; T cell receptor; adhesion; costimulation; T-CELL-RECEPTOR; ALDRICH-SYNDROME PROTEIN; TYROSINE-PHOSPHATASE INHIBITOR; PLASMA-MEMBRANE MICRODOMAINS; LEUKOCYTE INTEGRIN LFA-1; MATURE DENDRITIC CELLS; KINASE-C-THETA; ANTIGEN-RECEPTOR; CYTOPLASMIC DOMAIN; CONFORMATIONAL-CHANGES;
D O I
10.3389/fimmu.2016.00068
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It is well known that F-actin dynamics drive the micron-scale cell shape changes required for migration and immunological synapse (IS) formation. In addition, recent evidence points to a more intimate role for the actin cytoskeleton in promoting T cell activation. Mechanotransduction, the conversion of mechanical input into intracellular biochemical changes, is thought to play a critical role in several aspects of immunoreceptor triggering and downstream signal transduction. Multiple molecules associated with signaling events at the IS have been shown to respond to physical force, including the TCR, costimulatory molecules, adhesion molecules, and several downstream adapters. In at least some cases, it is clear that the relevant forces are exerted by dynamics of the T cell actomyosin cytoskeleton. Interestingly, there is evidence that the cytoskeleton of the antigen-presenting cell also plays an active role in T cell activation, by countering the molecular forces exerted by the T cell at the IS. Since actin polymerization is itself driven by TCR and costimulatory signaling pathways, a complex relationship exists between actin dynamics and receptor activation. This review will focus on recent advances in our understanding of the mechanosensitive aspects of T cell activation, paying specific attention to how F-actin-directed forces applied from both sides of the IS fit into current models of receptor triggering and activation.
引用
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页码:1 / 25
页数:25
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