The actin-bundling protein L-plastin supports T-cell motility and activation.

The actin-bundling protein L-plastin supports T-cell motility and activation.
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DOI:
10.1111/imr.12102
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发表时间:
2013-11
影响因子:
8.7
通讯作者:
Morley SC
Morley SC
中科院分区:
医学1区
文献类型:
--
作者:
Morley SC

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肌动蛋白动力学的严格调控对t细胞的运输和激活至关重要。最近对人类和小鼠T细胞的研究表明,T细胞的运动和完全T细胞激活需要造血特异性的肌动蛋白捆绑蛋白l -活蛋白。缺乏l -活蛋白的T细胞不能形成完全成熟的突触,因此细胞因子的产生和增殖减少。l -活蛋白表达的减少或丧失也会降低T细胞的速度,损害胸腺出口和结内运动。L-plastin对于近端t细胞受体和趋化因子受体信号传导是必不可少的,但对于突触成熟和细胞极化的后期阶段至关重要。丝氨酸磷酸化、钙和钙调蛋白结合调节t细胞受体和趋化因子受体结合后LPL的捆绑活性和定位。然而,这些调节结构域之间的相互作用以及由此导致的肌动蛋白细胞骨架结构局部控制的变化尚未完全阐明。间接证据表明l -活蛋白在整合素相关的粘附结构的形成或维持中起作用。由于L-plastin可能是常用免疫抑制剂地塞米松的靶点,因此充分阐明L-plastin在t细胞生物学中的调控和功能可能为临床有用的免疫治疗提供新的途径。
Tight regulation of actin dynamics is essential for T-cell trafficking and activation. Recent studies in human and murine T cells reveal that T-cell motility and full T-cell activation require the hematopoietic-specific, actin-bundling protein L-plastin. T cells lacking L-plastin do not form fully mature synapses and thus demonstrate reduced cytokine production and proliferation. Reduction or loss of L-plastin expression also reduces the velocity of T cells and impairs thymic egress and intranodal motility. While dispensable for proximal T-cell receptor and chemokine receptor signaling, L-plastin is critical to the later stages of synapse maturation and cellular polarization. Serine phosphorylation, calcium, and calmodulin binding regulate the bundling activity and localization of LPL following T-cell receptor and chemokine receptor engagement. However, the interaction between these regulatory domains and resulting changes in local control of actin cytoskeletal structures has not been fully elucidated. Circumstantial evidence suggests a function for L-plastin in either the formation or maintenance of integrin-associated adhesion structures. As L-plastin may be a target of the commonly used immunosuppressive agent dexamethasone, full elucidation of the regulation and function of L-plastin in T-cell biology may illuminate new pathways for clinically useful immunotherapeutics.
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