Microtubule association of the neuronal p35 activator of Cdk5
Microtubule association of the neuronal p35 activator of Cdk5
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DOI：
10.1074/jbc.c700052200
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发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Qi, Robert Z.
中科院分区：
文献类型：
--
作者：
Hou, Zhibo;Li, Qing;Qi, Robert Z.
Cdk5及其神经元激活剂p35在神经元迁移和大脑皮层正常发育中起重要作用。我们发现p35直接与α / β -微管蛋白和微管结合。微管聚合物而不是α / β -微管蛋白异源二聚体阻断p35与Cdk5的相互作用，从而抑制Cdk5-p35的活性。p25是一种神经毒素诱导的p35的截断形式，不具有微管蛋白和微管结合活性，Cdk5-p25对微管的抑制作用是惰性的。P35在促进微管组装和诱导微管束形成方面表现出较强的活性。此外，p35稳定的微管可以抵抗冷诱导的拆卸。在培养的皮质神经元中，p35的很大一部分定位于微管。当从大鼠脑提取物中分离微管时，p35与微管共组装，包括冷稳定的微管。总之，这些发现表明p35是一种调节微管动力学的微管相关蛋白。此外，微管在Cdk5活化的控制中起着重要作用。
Cdk5 and its neuronal activator p35 play an important role in neuronal migration and proper development of the brain cortex. We show that p35 binds directly to alpha/beta-tubulin and microtubules. Microtubule polymers but not the alpha/beta-tubulin heterodimer block p35 interaction with Cdk5 and therefore inhibit Cdk5-p35 activity. p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities, and Cdk5-p25 is inert to the inhibitory effect of microtubules. p35 displays strong activity in promoting microtubule assembly and inducing formation of microtubule bundles. Furthermore, microtubules stabilized by p35 are resistant to cold-induced disassembly. In cultured cortical neurons, a significant proportion of p35 localizes to microtubules. When microtubules were isolated from rat brain extracts, p35 co-assembled with microtubules, including cold-stable microtubules. Together, these findings suggest that p35 is a microtubule-associated protein that modulates microtubule dynamics. Also, microtubules play an important role in the control of Cdk5 activation.