Abstract
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.
Highlights
As a distinct member of the CDK family, Cdk5 is activated by a neuron-specific protein p35 or the p39 homologue of p35 in the central nervous system [1]
Studies in animal models have revealed their crucial involvements in neuronal migration during nervous system development as mice deficient of Cdk5 or p35 display abnormal brain cortex [3, 4]
The dynamic properties of microtubules are modulated through a sophisticated mechanism involving microtubule-associated proteins (MAPs),2
Summary
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. As a distinct member of the CDK family, Cdk is activated by a neuron-specific protein p35 or the p39 homologue of p35 in the central nervous system [1]. Cdk phosphorylates several MAPs including MAP1b, MAP2, tau, and doublecortin, mediating their association with microtubules and their microtubule-stabilizing functions [1, 6, 7]. It is poorly understood how Cdk activity is regulated. We have identified direct association of p35 with tubulin and microtubules and have shown the function of p35 as a MAP as well as the regulation of Cdk activation by microtubules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
