Balancing Axons and Dendrites

Abstract

Neurons are polarized cells with axons (signal output) and dendrites (signal input). Not only are these functionally distinct parts of the cell, but they differ in morphology too. Jiang et al. report that when glycogen synthase kinase 3β (GSK-3β) activity was increased by transfection of isolated embryonic hippocampal neurons with a constitutively active mutant, the number of cells that formed an axon decreased, and when GSK-3β activity was inhibited, the number of cells producing multiple axons increased even though the overall number of neurites did not change. They identified the phosphatidylinositol 3-kinase (PI3K) pathway as a stimulator of GSK-3β phosphorylation, which results in an inhibition of GSK-3β. Activation of the PI3K pathway by expression of the kinase Akt or inactivation of the phosphatase PTEN produced multiaxon neurons. Yoshimura et al. show that GSK-3β phosphorylates collapsin response mediator protein 2 (CRMP-2), which is known to contribute to axon formation. Treatment of neurons with neurotrophin 3 (NT-3) or brain-derived neurotrophic factor (BDNF) stimulated axon growth and decreased CRMP-2 phosphorylation. Furthermore, the stimulation in axon length was blocked if CRMP-2 abundance was decreased. Thus, a pathway involving PI3K regulates the activity of GSK-3β and the phosphorylation of the microtubule assembly regulatory protein CRMP-2 and hence controls axon formation and growth in neurons.—NG