Microtubule Dynamics

Microtubules are inherently dynamic, growing and shrinking in a process called “dynamic instability.” Microtubule growth (polymerization) occurs when individual tubulin dimers add individually to the ends of microtubules. The two ends of the microtubule are structurally distinct. The plus-end of the microtubule has the beta-subunit exposed and grows faster than the minus-end, that has the alpha subunit exposed.

The ends of microtubules have tubulin dimers with GTP at the E-site, causing them to have a straight conformation. When the GTP is hyrolyzed to GDP, as in the body of the microtubules, the dimer changes conformation to a bent back state. This bent back state destabilzes the microtubule structure.

If the very ends of the microtubule have GTP, then the microtubule will continue to grow. If the GTP cap is lost, the protofilaments will bend back and a rapid loss of polymer will occur making the individual filaments shrink.

Although dynamic instability is an inherent function of microtubules, it is highly regulated in the cell. We are interested in the fundamental question of how microtubule stabilizing proteins and destabilizing proteins can antagonistically function to control the length, growth, shrinkage, and stability of microtubules. We have new funding from the National Science Foundation, Division of Materials Research to study these questions with severing enzymes and stabilizing microtubule associated proteins separately and in tandem.

We are using in vitro reconstitution and direct microscopy imaging of individual microtubules during dynamic instability to systematically dissect how microtubules are controlled in cells.