Ligand-Dependent Concentric Actomyosin Arcs Regulate Tcr Mechano-Transduction At The Immunological Synapse
BIOPHYSICAL JOURNAL(2017)
摘要
T cell receptor (TCR) mechano-transduction is an emerging but poorly understood component of T cell activation. To define the contribution made by the cytoskeleton to TCR mechano-transduction, we investigated the role played by contractile actomyosin arcs populating the pSMAC region of the immunological synapse (IS) in ligand discrimination. Using super resolution microscopy, we show that the generation of organized actomyosin arcs depends on the ligand potency and the ability of non-muscle myosin II to contract actin filaments. While weak ligands induce disorganized actomyosin arcs, strong ligands result in organized actomyosin arcs that correlate well with tension-sensitive CasL phosphorylation and the accumulation of ligands at the IS center. Furthermore, the presence of ligand-dependent actomyosin arcs generates a dynamic range in the phosphorylation of the early signaling molecules. Taken together, our correlative study implicates ligand-dependent actomyosin arcs are a mechano-chemical feedback mechanism that amplifies the accumulation of critical signaling molecules at the IS.
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关键词
immunological synapse,ligand-dependent,mechano-transduction
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