Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation
Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation
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DOI：
10.1242/jcs.199042
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Sanchez-Madrid, Francisco
中科院分区：
文献类型：
--
作者：
Bustos-Moran, Eugenio;Blas-Rus, Noelia;Sanchez-Madrid, Francisco
免疫突触 (IS) 是在 T 淋巴细胞和抗原呈递细胞 (APC) 接触区域形成的特殊结构，对于适应性免疫反应至关重要。正确的 T 细胞激活需要其向 APC 极化，而 APC 高度依赖于微管蛋白细胞骨架。微管相关蛋白 4 (MAP4) 是一种微管 (MT) 稳定蛋白，可控制生理过程中的 MT，例如细胞分裂、迁移、囊泡运输或初级纤毛形成。在这项研究中，我们评估了 MAP4 在 T 细胞激活中的作用。 MAP4 装饰 T 细胞的中心体周围区域和 MT，并且参与响应 T 细胞激活的 MT 去酪氨酸化和稳定组装。此外，MAP4 促进 MT 组织中心 (MTOC) 向 IS 及时易位，以及维持 T 细胞激活的信号纳米囊泡的动态。然而，MAP4 充当其他 T 细胞激活相关信号的负调节因子，包括二酰甘油 (DAG) 产生和 IL2 分泌。我们的数据表明 MAP4 充当平衡 T 细胞激活的正负特征的检查点分子。
The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule-associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes, such as cell division, migration, vesicular transport or primary cilia formation. In this study, we assessed the role of MAP4 in T cell activation. MAP4 decorates the pericentrosomal area and MTs of the T cell, and it is involved in MT detyrosination and stable assembly in response to T cell activation. In addition, MAP4 prompts the timely translocation of the MT-organizing center (MTOC) towards the IS and the dynamics of signaling nanovesicles that sustains T cell activation. However, MAP4 acts as a negative regulator of other T cell activation-related signals, including diacylglycerol (DAG) production and IL2 secretion. Our data indicate that MAP4 acts as a checkpoint molecule that balances positive and negative hallmarks of T cell activation.