Bustos-Morán Eugenio, Blas-Rus Noelia, Martin-Cófreces Noa Beatriz, Sánchez-Madrid Francisco
Laboratory of Intercellular communication, Fundación CNIC, Madrid 28029, Spain.
Servicio de Inmunología, Hospital Universitario de la Princesa, UAM, IIS-IP, Madrid 28006, Spain.
J Cell Sci. 2017 Apr 1;130(7):1217-1223. doi: 10.1242/jcs.199042. Epub 2017 Feb 16.
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.
免疫突触（IS）是在T淋巴细胞与抗原呈递细胞（APC）之间的接触区域形成的一种特殊结构，对适应性免疫反应至关重要。T细胞的正常激活需要其向APC极化，这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，在细胞分裂、迁移、囊泡运输或初级纤毛形成等生理过程中控制微管。在本研究中，我们评估了MAP4在T细胞激活中的作用。MAP4分布于T细胞的中心体周围区域和微管上，并参与微管的去酪氨酸化和响应T细胞激活的稳定组装。此外，MAP4促使微管组织中心（MTOC）及时向免疫突触转运，并促进维持T细胞激活的信号纳米囊泡的动态变化。然而，MAP4作为其他T细胞激活相关信号的负调节因子，包括二酰基甘油（DAG）的产生和白细胞介素2（IL2）的分泌。我们的数据表明，MAP4作为一个检查点分子，平衡T细胞激活的正负特征。
