McNamara R K, Jiang Y, Streit W J, Lenox R H
Department of Psychiatry, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, PA 19104-6140, USA.
Neuroscience. 2000;97(3):581-9. doi: 10.1016/s0306-4522(00)00039-7.
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.
我们之前已经表明，富含豆蔻酰化丙氨酸的蛋白激酶C底物是大脑中一种主要的蛋白激酶C底物，可与丝状肌动蛋白结合并使其交联，在神经元生长锥中含量丰富，且在大脑中受发育调控。在此，我们研究了面神经切断或面神经切除损伤（这两种损伤会阻碍再生）后轴突再生过程中，以及逆行性神经毒素蓖麻毒素诱导运动神经元变性后，面神经运动核中富含豆蔻酰化丙氨酸的蛋白激酶C底物的表达情况。为作比较，我们同时检测了蛋白激酶C底物富含豆蔻酰化丙氨酸的蛋白激酶C底物样蛋白和生长相关蛋白43。富含豆蔻酰化丙氨酸的蛋白激酶C底物信使核糖核酸在面神经切断术后四天开始，在面神经运动核的神经元和非神经元细胞中均显著增加，在七天时达到峰值（增加2.5倍），到40天时降至基线水平。富含豆蔻酰化丙氨酸的蛋白激酶C底物蛋白在面神经切断术后四天和十四天测定时，在面神经运动核中同样升高了两倍。面神经切除后，富含豆蔻酰化丙氨酸的蛋白激酶C底物信使核糖核酸水平在七天时升高，到40天时恢复到基线水平。与富含豆蔻酰化丙氨酸的蛋白激酶C底物信使核糖核酸不同，富含豆蔻酰化丙氨酸的蛋白激酶C底物样信使核糖核酸水平在面神经切断或切除后的任何时间点，在面神经运动核中均未升高，而生长相关蛋白43信使核糖核酸在面神经切断或切除后，在面神经运动核神经元中迅速（一天）且持续（40天）升高。蓖麻毒素诱导的面神经运动神经元变性使小胶质细胞（凝集素阳性）和星形胶质细胞（胶质纤维酸性蛋白阳性）中的富含豆蔻酰化丙氨酸的蛋白激酶C底物和富含豆蔻酰化丙氨酸的蛋白激酶C底物样信使核糖核酸均升高。总体而言，这些数据表明，富含豆蔻酰化丙氨酸的蛋白激酶C底物在面神经损伤后的面神经运动核中呈现独特的表达模式，并且有人提出，富含豆蔻酰化丙氨酸的蛋白激酶C底物可能在神经再生和变性过程中，响应蛋白激酶C介导的信号传导，介导神经元和神经胶质细胞中的肌动蛋白-膜细胞骨架可塑性。
