Shackelford D A, Nelson K E
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624, USA.
J Neurochem. 1996 Jan;66(1):286-95. doi: 10.1046/j.1471-4159.1996.66010286.x.
The microtubule-associated protein tau plays an important role in the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. Ischemia disrupts the neuronal cytoskeleton both by promoting proteolysis of its components and by affecting kinase and phosphatase activities that alter its assembly. In this study the effect of ischemia and reperfusion on the expression and phosphorylation of tau was examined in a reversible model of spinal cord ischemia in rabbits. tau was found to be dephosphorylated in response to ischemia with a time course that closely matched the production of permanent paraplegia. Dephosphorylation of tau was limited to the caudal lumbar spinal cord. In a similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in the ischemic region. Thus, dephosphorylation of tau is an early marker of ischemia as is the rapid loss of Ca2+/calmodulin-dependent kinase II activity. tau, however, was rephosphorylated rapidly during reperfusion at site(s) that cause a reduction in its electrophoretic mobility regardless of the neurological outcome. Alterations in phosphorylation or degradation of tau may affect microtubule stability, possibly contributing to disruption of axonal transport but also facilitating neurite plasticity in a regenerative response.
微管相关蛋白tau在轴突生长和神经突可塑性所需的微管组装动力学中起重要作用。缺血通过促进其成分的蛋白水解以及影响改变其组装的激酶和磷酸酶活性来破坏神经元细胞骨架。在本研究中，在兔脊髓缺血的可逆模型中检测了缺血和再灌注对tau表达和磷酸化的影响。发现tau响应缺血而发生去磷酸化，其时间进程与永久性截瘫的产生密切匹配。tau的去磷酸化仅限于尾侧腰段脊髓。同样，钙调蛋白依赖性激酶II活性仅在缺血区域降低。因此，tau的去磷酸化是缺血的早期标志物，钙调蛋白依赖性激酶II活性的快速丧失也是如此。然而，无论神经学结果如何，tau在再灌注期间在导致其电泳迁移率降低的位点迅速重新磷酸化。tau磷酸化或降解的改变可能影响微管稳定性，这可能导致轴突运输中断，但也有助于再生反应中的神经突可塑性。
