The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles.
The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles.
复制标题
DOI：
10.1371/journal.pone.0089796
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ihara Y
中科院分区：
文献类型：
--
作者：
Xie C;Miyasaka T;Yoshimura S;Hatsuta H;Yoshina S;Kage-Nakadai E;Mitani S;Murayama S;Ihara Y
微管相关蛋白2（Microtubule-associated protein 2，MAP 2）和Tau蛋白是神经元中大量存在的微管相关蛋白。这两种蛋白质具有高度同源的羧基末端序列，作为微管结合结构域的功能。尽管Tau被广泛接受为人类tau蛋白病（包括阿尔茨海默病（AD））中的病理病因因子，但不知道MAP 2与tau蛋白病之间是否存在关系。为了更好地理解MAP 2和Tau的病理作用，我们比较了它们在转基因秀丽隐杆线虫中的行为，其中MAP 2或Tau在泛神经元上表达。MAP 2和Tau均引起严重的神经元功能障碍和神经炎异常，尽管在蠕虫神经元中不存在洗涤剂不溶性聚集体。生物化学分析显示，在蠕虫中表达的MAP 2或Tau是高度磷酸化的，并且不与微管结合。新提出的有效区分MAP 2和Tau的高度同源羧基末端序列的MAP 2抗体表明，MAP 2不参与AD脑中神经元缠结的生长过程。这些结果表明，Tau和MAP 2在包涵体形成中具有不同的命运，并提高了MAP 2在AD脑中的神经毒性中起重要作用的可能性，尽管不存在MAP 2聚集体。
Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy. To better understand the pathological roles of MAP2 and Tau, we compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal dysfunction and neuritic abnormalities, despite the absence of detergent-insoluble aggregates in worm neurons. Biochemical analysis revealed that the expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to microtubules. Newly raised antibodies to MAP2 that effectively distinguished between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed that MAP2 was not involved in the growth process of neurofibrillary tangles in the AD brain. These results indicate that Tau and MAP2 have different fates in the inclusion formation and raise the possibility that MAP2 plays a significant role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates.
登录
查看更多内容
影响因子：
6.1
作者：
Miyasaka, T;Ding, Z;Ihara, Y
通讯作者：
Ihara, Y
影响因子：
3.5
作者：
Fatouros, Chronis;Pir, Ghulam Jeelani;Baumeister, Ralf
通讯作者：
Baumeister, Ralf
影响因子：
4.2
作者：
Brandt, Roland;Gergou, Aikaterini;Hutter, Harald
通讯作者：
Hutter, Harald
在轴突和微管相关蛋白2C中的TAU选择性稳定在细胞体和树突中有助于成熟神经元中细胞骨架蛋白的极化定位。
影响因子：
7.8
作者：
Hirokawa, N;Funakoshi, T;SatoHarada, R;Kanai, Y
通讯作者：
Kanai, Y
影响因子：
16.2
作者：
KONDO, J;HONDA, T;IHARA, Y
通讯作者：
IHARA, Y