Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation.
Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation.
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DOI：
10.1111/imr.12123
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发表时间：
2013-11
影响因子：
8.7
通讯作者：
Burkhardt JK
中科院分区：
文献类型：
--
作者：
Babich A;Burkhardt JK
Ca2+动员和细胞骨架重组是t细胞活化的关键标志，它们之间的相互依赖性早已被认识到。该领域的最新进展已经阐明了这些事件背后的分子途径，并揭示了几个交叉点。Ca2+信号传导可分为两个阶段：导致Ca2+从内质网储存释放的初始事件，以及涉及STIM 1（基质相互作用分子1）聚集和CRAC（钙释放激活钙）通道激活的第二阶段。细胞骨架动力学促进这两个阶段。在第一阶段，肌动蛋白细胞骨架促进t细胞受体的机械转导，并作为微团簇组装的动态支架。驱动肌动蛋白聚合的蛋白，如WASp （wiskot - aldrich综合征蛋白）和HS1（造血谱系细胞特异性蛋白1），通过磷脂酶Cγ1 （PLCγ1）促进信号传导，并从内质网储存中释放Ca2+。在第二阶段，WAVE （wasp家族verprolin同源蛋白）复合物和微管细胞骨架促进STIM - 1在质膜附着位点聚集，打开Orai通道。此外，总的细胞形状变化和细胞器运动缓冲局部Ca2+水平，导致持续的Ca2+动员。相反，升高的细胞内Ca2+激活细胞骨架重塑。这可以通过钙蛋白酶活性间接发生，也可以通过Ca2+依赖的细胞骨架调节蛋白（如肌球蛋白II和l -活蛋白）直接发生。虽然细胞骨架确实调节Ca2+反应，反之亦然，但Ca2+和细胞骨架之间的相互依赖也包括在共享中间体的下游平行发生的信号事件。plc - γ - 1裂解肌醇同时触发内质网储存释放和二酰基甘油依赖的微管组织中心重新定向，同时耗尽磷脂酰肌醇-4,5-二磷酸池，这是多种肌动蛋白调节蛋白的激活剂。T细胞中Ca2+信号和细胞骨架动力学的密切相互依赖为T细胞激活提供了正反馈机制，并允许对细胞外信号进行精细调节。
Ca2+ mobilization and cytoskeletal reorganization are key hallmarks of T-cell activation, and their interdependence has long been recognized. Recent advances in the field have elucidated the molecular pathways that underlie these events and have revealed several points of intersection. Ca2+ signaling can be divided into two phases: initial events leading to release of Ca2+ from endoplasmic reticulum stores, and a second phase involving STIM 1 (stromal interaction molecule 1) clustering and CRAC (calcium-release activation calcium) channel activation. Cytoskeletal dynamics promote both phases. During the first phase, the actin cytoskeleton promotes T-cell receptor mechanotransduction and serves as a dynamic scaffold for microcluster assembly. Proteins that drive actin polymerization such as WASp (Wiskott-Aldrich syndrome protein) and HS1 (hematopoietic lineage cell-specific protein 1) promote signaling through PLCγ1 (phospholipase Cγ1) and release of Ca2+ from endoplasmic reticulum stores. During the second phase, the WAVE (WASP-family verprolin homologous protein) complex and the microtubule cytoskeleton promote STIM 1 clustering at sites of plasma membrane apposition, opening Orai channels. In addition, gross cell shape changes and organelle movements buffer local Ca2+ levels, leading to sustained Ca2+ mobilization. Conversely, elevated intracellular Ca2+ activates cytoskeletal remodeling. This can occur indirectly, via calpain activity, and directly, via Ca2+-dependent cytoskeletal regulatory proteins such as myosin II and L-plastin. While it is true that the cytoskeleton regulates Ca2+ responses and vice versa, interdependence between Ca2+ and the cytoskeleton also encompasses signaling events that occur in parallel, downstream of shared intermediates. Inositol cleavage by PLCγ1 simultaneously triggers both endoplasmic reticulum store release and diacylglycerol-dependent microtubule organizing center reorientation, while depleting the pool of phosphatidylinositol-4,5-bisphosphate, an activator of multiple actin regulatory proteins. The close interdependence of Ca2+ signaling and cytoskeletal dynamics in T cells provides positive feedback mechanisms for T-cell activation and allows for finely tuned responses to extracellular cues.
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影响因子：
3.7
作者：
Chen EJ;Shaffer MH;Williamson EK;Huang Y;Burkhardt JK
通讯作者：
Burkhardt JK
DOI：
10.1083/jcb.201201018
发表时间：
2012-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Babich A;Li S;O'Connor RS;Milone MC;Freedman BD;Burkhardt JK
通讯作者：
Burkhardt JK
影响因子：
4.8
作者：
Ben-Aissa, Khadija;Patino-Lopez, Genaro;Shaw, Stephen
通讯作者：
Shaw, Stephen
影响因子：
4.4
作者：
Arrieumerlou, C;Randriamampita, C;Trautmann, A
通讯作者：
Trautmann, A
影响因子：
11.4
作者：
Baixauli, Francesc;Martin-Cofreces, Noa B.;Sanchez-Madrid, Francisco
通讯作者：
Sanchez-Madrid, Francisco