Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression.
Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression.
复制标题
面部运动神经元再生诱导肉豆蔻酰化富含丙氨酸的 C 激酶底物表达的独特空间和时间模式。
DOI：
10.1016/s0306-4522(00)00039-7
复制
发表时间：
2000
期刊：
影响因子：
3.3
通讯作者：
Lenox,RH
中科院分区：
文献类型：
--
作者：
McNamara,RK;Jiang,Y;Streit,WJ;Lenox,RH
我们之前已经证明，脑内一种结合并交联丝状肌动蛋白的初级蛋白激酶C底物——肉豆蔻酰化的富丙氨酸C激酶底物在神经元生长锥中丰富，并在脑内受到发育调节。在这里，我们检测了面部运动核中肉豆酰化的富含丙氨酸的C激酶底物在面神经轴突再生过程中的表达，在面神经轴突切除或面神经切除病变后，阻碍再生，或在逆行神经毒素蓖麻毒素诱导的运动神经元变性后。为了进行比较，我们平行研究了蛋白激酶C底物肉豆蔻酰基化富丙氨酸C激酶底物样蛋白和生长相关蛋白-43。肉豆蔻酰基化富含丙氨酸的C激酶底物信使RNA在面部运动核的神经元和非神经元细胞中表现出强劲的增加，在切开后4天开始，在第7天达到峰值（2.5倍），并在第40天回落到基线水平。肉豆蔻酰基化富含丙氨酸的C激酶底物蛋白在轴切开术后4天和14天在面部运动核中同样表现出两倍的升高。神经切除后，肉豆蔻酰基化富丙氨酸C激酶底物信使RNA水平在第7天升高，并在第40天恢复到基线水平。与肉豆蔻酰化富丙氨酸C激酶底物信使RNA不同，在神经轴切或切除后的任何时间点，面部运动核中的肉豆蔻酰化富丙氨酸C激酶底物样信使RNA水平都没有增加，而在神经轴切或切除后的面部运动核神经元中，生长相关蛋白43信使RNA表现出快速（1天）和延长（40天）的升高。蓖麻毒素诱导的面部运动神经元变性升高了小胶质细胞（凝集素阳性）和星形胶质细胞（胶质纤维酸性蛋白阳性）中肉豆蔻酰化富丙氨酸C激酶底物和肉豆蔻酰化富丙氨酸C激酶底物样信使rna。总的来说，这些数据表明，肉豆蔻酰化富丙氨酸C激酶底物在面神经病变后的面神经运动核中表现出独特的表达谱，并且提出，肉豆蔻酰化富丙氨酸C激酶底物可能在神经再生和变性过程中响应蛋白激酶介导的信号传导，介导神经元和胶质细胞的肌动蛋白膜细胞骨架可塑性。
We have previously shown that the myristoylated alanine-rich C kinase substrate, a primary protein kinase C substrate in brain that binds and cross-links filamentous actin, is enriched in neuronal growth cones and is developmentally regulated in brain. Here we examined myristoylated alanine-rich C kinase substrate expression in the facial motor nucleus during axonal regeneration following facial nerve axotomy or facial nerve resection lesions, which impede regeneration, or following motor neuron degeneration induced by the retrograde neurotoxin ricin. For comparative purposes, the protein kinase C substrates myristoylated alanine-rich C kinase substrate-like protein and growth-associated protein-43 were examined in parallel. Myristoylated alanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days. Myristoylated alanine-rich C kinase substrate protein similarly exhibited a twofold elevation in the facial motor nucleus determined four and 14 days post-axotomy. Following nerve resection, myristoylated alanine-rich C kinase substrate messenger RNA levels increased at seven days and returned to baseline levels by 40 days. Unlike myristoylated alanine-rich C kinase substrate messenger RNA, myristoylated alanine-rich C kinase substrate-like messenger RNA levels did not increase in the facial motor nucleus at any time point following nerve axotomy or resection, whereas growth-associated protein-43 messenger RNA exhibited a rapid (one day) and prolonged (40 days) elevation in facial motor nucleus neurons following either nerve axotomy or resection. Ricin-induced degeneration of facial motor neurons elevated myristoylated alanine-rich C kinase substrate and myristoylated alanine-rich C kinase substrate-like messenger RNAs in both microglia (lectin-positive) and astrocytes (glial fibrillary acidic protein-positive). Collectively, these data demonstrate that myristoylated alanine-rich C kinase substrate exhibits a unique expression profile in the facial motor nucleus following facial nerve lesions, and it is proposed that myristoylated alanine-rich C kinase substrate may serve to mediate actin-membrane cytoskeletal plasticity in both neurons and glial cells in response to protein kinaseC-mediated signaling during nerve regeneration and degeneration.