Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons

GUSTAVO PIGINO, GABRIELA PAGLINI, LUIS ULLOA, JESÚS AVILA AND ALFREDO CÁCERES

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Lugar: Cambridge; Año: 1997 vol. 110 p. 257 - 270

0021-9533

Cultures of cerebellar macroneurons were used to study theexpression, activity, subcellular localization, and functionof cdk5 during neuronal morphogenesis. The resultsobtained indicate that in non-polarized neurons cdk5 isrestricted to the cell body but as soon as polarity is establishedit becomes highly concentrated at the distal tip ofgrowing axons where it associates with microtubules andthe subcortical cytoskeleton. In addtion, we show thatlaminin, an extracellular matrix molecule capable of stimulatingaxonal extension and promoting MAP1b phosphorylation(DiTella et al., 1996), accelerates the redistributionof cdk5 to the axonal tip and dramatically increases itsactivity. Finally, our results indicate that cdk5 suppressionby antisense oligonucleotide treatment selectively reducesaxonal elongation and decreases the phosphorylation statusof MAP1b, as well as its binding to microtubules. Takencollectively, our observations suggest that cdk5 may serveas an important regulatory linker between enviromentalsignals (e.g. laminin) and constituents of the intracellularmachinery (e.g. MAP1b) involved in axonal formation.