Eph receptor tyrosine kinases regulate astrocyte cytoskeletal rearrangement and focal adhesion formation
Eph receptor tyrosine kinases regulate astrocyte cytoskeletal rearrangement and focal adhesion formation
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DOI：
10.1111/j.1471-4159.2010.06655.x
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发表时间：
2010-05-01
影响因子：
4.7
通讯作者：
Turnley, Ann M.
中科院分区：
文献类型：
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作者：
Puschmann, Till B.;Turnley, Ann M.
P>EphA4 缺失小鼠在脊髓损伤后星形胶质细胞增生受损。这可能是因为细胞骨架调节的改变，并且本文使用来自野生型和EphA4缺失小鼠的培养的星形胶质细胞进行检查。在基础条件下，EphA4 缺失的星形胶质细胞看起来相对正常，但在刺激导致细胞骨架重排后，EphA4 缺失的细胞反应更慢。当使用 Rho 激酶抑制剂 HA1077 使 F-肌动蛋白应力纤维塌陷时，较少的 EphA4 无效细胞响应 HA1077 显示应力纤维塌陷，并且在去除 HA1077 后恢复应力纤维的速度更慢。 EphA4无效星形胶质细胞的粘附性较差，粘着斑也较小，而肝配蛋白-A5-Fc激活Eph受体则增加了血清饥饿后野生型和敲除星形胶质细胞中粘着斑的数量。使用划痕伤口检测，侵入划痕的 EphA4 缺失星形胶质细胞显示神经胶质原纤维酸性蛋白表达受损，特别是在增殖细胞中。星形胶质细胞不表达 Ephexin（一种与 Eph 相互作用的主要 Rho 鸟嘌呤交换因子），但它们表达 Vav 蛋白，与野生型星形胶质细胞相比，EphA4 null 中磷酸 Vav 的水平较低。这可能导致 EphA4 无效星形胶质细胞中通常观察到的较慢的细胞骨架反应。因此，Eph 受体信号传导通过调节细胞骨架反应来调节星形胶质细胞的反应性。
P>EphA4 null mice have impaired astrocytic gliosis following spinal cord injury. This may be because of altered cytoskeletal regulation and is examined herein using cultured astrocytes from wildtype and EphA4 null mice. Under basal conditions EphA4 null astrocytes appeared relatively normal but following stimuli resulting in cytoskeletal rearrangement, EphA4 null cells responded more slowly. When F-actin stress fibers were collapsed using the Rho kinase inhibitor HA1077, fewer EphA4 null cells showed stress fiber collapse in response to HA1077 and recovered stress fibers more slowly following HA1077 removal. EphA4 null astrocytes were less adherent and had smaller focal adhesions, while activation of Eph receptors with ephrin-A5-Fc increased the numbers of focal adhesions in both wildtype and knockout astrocytes following serum starvation. Using scratch wound assays, EphA4 null astrocytes invading the scratch showed impaired glial fibrillary acidic protein expression, particularly in proliferative cells. Astrocytes did not express Ephexin, a major Eph-interacting Rho guanine exchange factor, but they expressed Vav proteins, with lower levels of phospho-Vav in EphA4 null compared to wildtype astrocytes. This may contribute to the slower cytoskeletal responses generally observed in the EphA4 null astrocytes. Eph receptor signaling therefore regulates astrocyte reactivity through modulation of cytoskeletal responses.