PKCε induces astrocyte stellation by modulating multiple cytoskeletal proteins and interacting with Rho A signalling pathways:: implications for neuroinflammation
PKCε induces astrocyte stellation by modulating multiple cytoskeletal proteins and interacting with Rho A signalling pathways:: implications for neuroinflammation
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DOI：
10.1111/j.1460-9568.2007.05364.x
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Tranque, Pedro
中科院分区：
文献类型：
--
作者：
Burgos, Miguel;Calvo, Soledad;Tranque, Pedro
尽管星形对维持星形胶质细胞的功能很重要，但控制这些细胞形态的细胞内信号却很少被表征。我们的目的是研究蛋白激酶C epsilon （PKC epsilon）在星形胶质细胞星形中的意义。我们发现，暴露于促炎剂脂多糖诱导的星形胶质细胞的形态转变被野生型PKC epsilon的腺病毒表达增强，PKC epsilon的激活足以引发戏剧性的星形。这种作用是由细胞生长过程中微管和胶质原纤维酸性蛋白细丝的重排、应力纤维的破坏和新肌动蛋白细丝的形成所介导的。此外，PKC epsilon调节肌动蛋白相互作用元件，如非肌球蛋白和ezrin/radixin/moesin家族的蛋白质。我们还观察到PKC epsilon的至少部分作用取决于其催化活性。最后，PKC epsilon的星形化可以通过一种与扁平星形细胞形态稳定性有关的Rho a的组成活性形式的表达来阻止。总之，PKC epsilon是星形胶质细胞形态可塑性的关键细胞内调节剂，影响大范围的细胞骨架元件并使Rho a依赖性通路失活。PKC epsilon的这些形态学影响可能在神经炎症过程中起重要作用。
Despite the importance of stellation to maintain astrocyte functionality, the intracellular signals controlling morphology in these cells are poorly characterized. Our goal was to examine the implication of protein kinase C epsilon (PKC epsilon) in astrocyte stellation. We found that the morphological transformation of astrocytes induced by exposure to the pro-inflammatory agent lipopolysaccharide is enhanced by adenoviral expression of wild-type PKC epsilon, and that activation of PKC epsilon is sufficient to trigger a dramatic stellation. Such an effect is mediated by the rearrangement of microtubules and filaments of glial fibrillary acidic protein, disorganization of stress fibres, and formation of new actin filaments within growing cellular processes. Furthermore, PKC epsilon regulates actin-interacting elements such as non-muscle myosin and proteins of the ezrin/radixin/moesin family. We also observed that at least part of the actions of PKC epsilon depend on its catalytic activity. Finally, stellation by PKC epsilon could be blocked by the expression of a constitutively active form of Rho A implicated in the stability of the flat astrocytic morphology. In summary, PKC epsilon stands out as a key intracellular regulator of morphological plasticity in astrocytes, affecting a large range of cytoskeletal elements and inactivating Rho A-dependent pathways. These morphological effects of PKC epsilon may play essential roles during the course of neuroinflammation.