ANALYSIS OF THE EXPRESSION, DISTRIBUTION AND FUNCTION OF CYCLIN-DEPENDENT KINASE-5 (CDK5) IN DEVELOPING CEREBELLAR MACRONEURONS

Cultures of cerebellar macroneurons were used to study the expression, activity, subcellular localization, and function of cdk5 during neuro nal morphogenesis. The results obtained indicate that in non-polarized neurons cdk5 is restricted to the cell body but as soon as polarity i s established it becomes highly concentrated at the distal tip of grow ing axons where it associates with microtubules and the subcortical cy toskeleton. In addtion, we show that laminin, an extracellular matrix molecule capable of stimulating axonal extension and promoting MAP1b p hosphorylation (DiTella et al., 1996), accelerates the redistribution of cdk5 to the axonal tip and dramatically increases its activity. Fin ally, our results indicate that cdk5 suppression by antisense oligonuc leotide treatment selectively reduces axonal elongation and decreases the phosphorylation status of MAP1b, as well as its binding to microtu bules. Taken collectively, our observations suggest that cdk5 may serv e as an important regulatory linker between enviromental signals (e.g. laminin) and constituents of the intracellular machinery (e.g. MAP1b) involved in axonal formation.