Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
J Cell Biol. 2012 Sep 17;198(6):1025-37. doi: 10.1083/jcb.201202137.
T cell antigen receptor-proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we find that a subset of microtubules became rapidly stabilized and that their α-tubulin subunit posttranslationally detyrosinated after engagement of the T cell receptor. Formation of stabilized, detyrosinated microtubules required the formin INF2, which was also found to be essential for centrosome reorientation, but it occurred independently of T cell receptor-induced massive tyrosine phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in centrosome repositioning, was able to mediate the formation of stable, detyrosinated microtubules and to restore centrosome translocation in DIA1-, FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that microtubule stabilization was required for centrosome polarization. Our work identifies INF2 and stable, detyrosinated microtubules as central players in centrosome reorientation in T cells.
T 细胞抗原受体近端信号成分、Rho 家族 GTPases、formin 蛋白 DIA1 和 FMNL1 已被牵连到 T 淋巴细胞免疫突触中心体的重定向中。然而，这些分子在重定向过程中的作用尚不清楚。在这里，我们发现一组微管迅速稳定，并且它们的α-微管蛋白亚基在 T 细胞受体结合后发生了翻译后去酪氨酸化。稳定的、去酪氨酸化的微管的形成需要formin INF2，它也被发现对中心体重定向至关重要，但它发生在 T 细胞受体诱导的大量酪氨酸磷酸化之前。FH2 结构域被映射为参与中心体重定位的 INF2 区域，能够介导稳定的、去酪氨酸化的微管的形成，并在 DIA1、FMNL1、Rac1 和 Cdc42 缺陷细胞中恢复中心体易位。进一步的实验表明，微管稳定对于中心体极化是必需的。我们的工作确定了 INF2 和稳定的、去酪氨酸化的微管是 T 细胞中中心体重定向的核心参与者。
