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 á/â-tubulin and microtubules. Microtubule polymers but not the á/â-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.

Item Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Cellular nervous system
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Cheung, NS (Dr Nam Cheung)
ID Code:	61630
Year Published:	2007
Web of Science® Times Cited:	32
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2010-03-04
Last Modified:	2010-05-04
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