Initiation of T cell signaling by CD45 segregation at 'close contacts'.
Initiation of T cell signaling by CD45 segregation at 'close contacts'.
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DOI：
10.1038/ni.3392
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发表时间：
2016-05
影响因子：
30.5
通讯作者：
Davis SJ
中科院分区：
文献类型：
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作者：
Chang VT;Fernandes RA;Ganzinger KA;Lee SF;Siebold C;McColl J;Jönsson P;Palayret M;Harlos K;Coles CH;Jones EY;Lui Y;Huang E;Gilbert RJC;Klenerman D;Aricescu AR;Davis SJ
已经提出激酶和酪氨酸磷酸酶CD 45的局部分离是T细胞受体（TCR）触发的基础，但分离如何发生以及它是否可以启动信号传导尚不清楚。使用结构和生物物理分析，我们表明，CD 45的细胞外区域是刚性的，并延伸超出TCR-配体复合物跨越的距离，这意味着TCR-配体接合的位点将在空间上排除CD 45。我们还表明，形成新的结构，其特征在于自发的亚微米尺度的CD 45和激酶分离，称为“紧密接触”，启动信号，即使当TCR配体不存在。我们的工作揭示了局部CD 45和激酶分离的结构基础和意想不到的有效信号作用。TCR配体可以通过保持受体紧密接触来增强信号传导。
It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell receptor (TCR) triggering, but how segregation would occur and whether it can initiate signaling is unclear. Using structural and biophysical analysis we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of new structures characterized by spontaneous sub-micron scale CD45 and kinase segregation, called ‘close-contacts’, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the unexpectedly potent signaling effects of local CD45 and kinase segregation. TCR ligands could heighten signaling simply by holding receptors in close-contacts.