Regulation of Kinesin: Implications for Neuronal Development

Rapid organelle transport is required for process growth and establishment of specialized structures during neuronal development. Furthermore, maintenance of mature neuronal architecture and function depends on the proper delivery of materials to specialized domains within axons, such as nodes of Ranvier and synaptic terminals. Kinesin is the most abundant member of the kinesin superfamily of microtubule-based motors. Kinesins are responsible for anterograde transport of an assortment of membrane-bound organelles in all cell types. Kinesin is enriched in neurons, but relatively little is known about the developmental regulation of its expression, localization, and function in nervous tissue. By examining kinesin expression in developing brain and in cultures of cortical neurons, we found that kinesin is enriched in elongating neurites, including their growing tips, the growth cones. To gain understanding of mechanisms that underlie the delivery of proteins to specific cellular subcompartments, we focused on studying modifications on kinesin that lead to its dissociation from membranes. Since kinesin is a phosphoprotein in vivo, we evaluated the correlation between kinesin phosphorylation and its membrane association and identified a number of kinases which phosphorylate kinesin and alter its function.