Cyclin-Dependent Kinase 5 Permits Efficient Cytoskeletal Remodeling—a Hypothesis on Neuronal Migration

Migration of neurons to their proper position underlies mammalian brain development. To remain on the proper path, a migrating neuron needs to detect various external signals and respond by efficiently remodeling its cytoskeleton. Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, regulates neuronal migration by phosphorylating a number of intracellular substrates. Deficiencies in Cdk5 preferentially cause impairments in radial glia-guided migration, a process that involves complex remodeling of the cytoskeleton, particularly the microtubules. Furthermore, the defined substrates of Cdk5 that are important for migration generally link Cdk5 to the cytoskeleton. Interestingly, none of these phosphorylation events seem to directly control the activity of the substrates. Taken together, these findings support a model in which Cdk5 does not directly control the detection of any specific external signals but instead regulates efficient remodeling of the cytoskeleton through phosphorylation of multiple substrates.