Morphogenesis and the control of microtubule dynamics in cells

Microtubules show unusual dynamic properties at steady state in vitro. While overall the polymer mass remains stable, individual polymers in the population are either growing or shrinking. This phenomenon called dynamic instability is best explained by the known coupling of polymerization to GTP hydrolysis, and the hypothesis that the stability or instability of the whole polymer is determined by whether GTP or GDP is bound to the terminal subunit. Similar unusual dynamics have now also been found in vivo. By visualizing new subunit assembly after injection of tubulin modified with biotin into living fibroblast cells, we can visualize new growth on individual microtubules with antibody to biotin. Microtubules grow in vivo at about 4 microns min-1 and after rapid and precessive depolymerization old microtubules are replaced by new growth from the centrosome. Some microtubules turn over much more slowly and these stable microtubules have a different spatial distribution from the majority of dynamic ones. The existence of both stable and dynamic microtubules in the same cell suggests a model for morphogenesis of the microtubule cytoskeleton. The rapid turnover of microtubules in the cell provides a complex population upon which selective factors can act. Stability can be generated at the end of the polymer and affects the entire microtubule. This model of selective stabilization at the microtubule ends is discussed in terms of recent experiments on the establishment of kinetochore-pole microtubules during mitosis.