A new perspective on microtubules and axon growth.

Abstract

Role of the cell body in generating the axonal microtubule ar- ray, whereas the other emphasizes the role of local mecha- nisms within the axon itself. Recent work suggests that events significant to the generation of the axonal microtubule array occur within both of these compartments, and that axon growth is dependent upon the coordinated efforts of several types of microtubule behavior. Our goal in this article is to evaluate the existing models in light of more recent data, and provide new perspectives on the manner by which the axonal microtubule array is generated. Evidence Supporting a Role for the Cell Body The first comprehensive model for axon growth was put forth by Lasek and collaborators over a decade ago, and was based on the kinetics of tubulin transport from the cell body into and down the axon. In these experiments, radiolabeled amino acids were injected into the cell bodies of neurons to radioactively tag the newly synthesized proteins. The move- ment of these proteins into and down the axon was then ana- lyzed and quantified using a biochemical method. After vari- ous time intervals, the axon was cut into segments and the protein composition of each segment was resolved using SDS-PAGE. Then, levels of radioactivity were measured in bands corresponding to specific proteins, one of which was tubulin. These experiments showed that the movement of newly synthesized tubulin down the axon occurs as a discrete wave traveling at a rate (=1 nun/d) that is inconsistent with diffusive movement. Moreover, the radiolabeled tubulin was not extractable under conditions that removed unpolymer- ized mbulin, suggesting that tubulin is transported in an as- sembled form. Based on these data, Lasek and collaborators proposed that microtubules destined for the axon are preas-