EVIDENCE FOR THE PARTICIPATION OF THE NEURON-SPECIFIC CDK5 ACTIVATOR P35 DURING LAMININ-ENHANCED AXONAL GROWTH

Cultures of cerebellar macroneurons were used to study the pattern of expression, subcellular localization, and function of the neuronal cdk 5 activator p35 during laminin-enhanced axonal growth. The results obt ained indicate that laminin, an extracellular matrix molecule capable of selectively stimulating axonal extension and promoting MAP1B phosph orylation at a proline-directed protein kinase epitope, selectively st imulates p35 expression, increases its association with the subcortica l cytoskeleton, and accelerates its redistribution to the axonal growt h cones. Besides, suppression of p35, but not of a highly related isof orm designated as p39, by antisense oligonucleotide treatment selectiv ely reduces cdk5 activity, laminin-enhanced axonal elongation, and MAP 1b phosphorylation. Taken collectively, the present results suggest th at cdk5/p35 may serve as an important regulatory linker between enviro nmental signals (e.g., laminin) and constituents of the intracellular machinery (e.g., MAP1B) involved in axonal elongation.