Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse
Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse
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DOI：
10.1002/eji.200323858
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发表时间：
2003-03-01
影响因子：
5.4
通讯作者：
Tybulewicz, VLJ
中科院分区：
文献类型：
--
作者：
Ardouin, L;Bracke, M;Tybulewicz, VLJ
APC上的肽- mhc复合物通过TCR激活T系细胞，严重依赖于肌动蛋白细胞骨架的重排。Vav1是gtpase Rho/Rac家族成员的鸟嘌呤核苷酸交换因子，该家族成员在TCR刺激后被激活，这表明它可能将TCR信号转导激活部分或全部肌动蛋白控制的过程。我们发现，与野生型细胞相比，vav1缺陷双阳性胸腺细胞与APC呈递激动剂肽形成结合物的效率较低。此外，我们证明了Vav1是tcr诱导的整合素LFA-1激活所必需的，这可能解释了共轭形成的缺陷。然而，一旦vav1缺陷细胞形成偶联物，蛋白质在偶联物界面组装成免疫突触是正常的。相反，胸腺细胞极化在Vav1缺失的情况下是有缺陷的，这可以通过微管组织中心的重新定位来判断。这些数据表明，Vav1仅将信号转导到免疫突触中细胞骨架依赖事件的子集。
Activation of T lineage cells through the TCR by peptide-MHC complexes on APC is critically dependent on rearrangement of the actin cytoskeleton. Vav1 is a guanine nucleotide exchange factor for members of the Rho/Rac family of GTPases which is activated following TCR stimulation, suggesting that it may transduce TCR signals to the activation of some or all actin-controlled processes. We show that Vav1-deficient double-positive thymocytes are less efficient at forming conjugates with APC presenting agonist peptide than wild-type cells are. Furthermore we demonstrate that Vav1 is required for TCR-induced activation of the integrin LFA-1, which is likely to explain the defect in conjugate formation. However, once Vav1-deficient cells form a conjugate, the assembly of proteins into an immunological synapse at the conjugate interface is normal. In contrast, thymocyte polarization is defective in the absence of Vav1, as judged by the relocalization of the microtubule-organizing center. These data demonstrate that Vav1 transduces signals to only a subset of cytoskeleton-dependent events at the immunological synapse.