JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins
JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins
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DOI：
10.1016/s1534-5807(03)00094-7
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发表时间：
2003-04-01
影响因子：
11.8
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Chang, LF;Jones, Y;Karin, M
微管（MT）在轴突和树突过程的形成和维持中起着重要作用。MT动力学受MT相关蛋白（MAP）的调节，其活性受蛋白磷酸化的调节。我们发现，c-Jun氨基末端蛋白激酶（JNK）的MAP激酶，JNK 1亚组的成员，参与调节MT在神经元细胞中的动力学。JNK 1（-/-）小鼠表现出破坏前连合束形成和轴突和树突内MT的进行性损失。MAP 2和MAP 1B多肽在JNK 1（-/-）脑中低磷酸化，导致结合MT和促进其组装的能力受损。这些结果表明JNK 1是维持神经元细胞骨架完整性所必需的，并且是MAP活性和MT组装的关键调节剂。
Microtubules (MTs) play an important role in elaboration and maintenance of axonal and dendritic processes. MT dynamics are modulated by MT-associated proteins (MAPs), whose activities are regulated by protein phosphorylation. We found that a member of the c-Jun NH2-terminal protein kinase (JNK) subgroup of MAP kinases, JNK1, is involved in regulation of MT dynamics in neuronal cells. Jnk1(-/-) mice exhibit disrupted anterior commissure tract formation and a progressive loss of MTs within axons and dendrites. MAP2 and MAP1B polypeptides are hypophosphorylated in Jnk1(-/-) brains, resulting in compromised ability to bind MTs and promote their assembly. These results suggest that JNK1 is required for maintaining the cytoskeletal integrity of neuronal cells and is a critical regulator of MAP activity and MT assembly.