Background: What are Microtubules?

Microtubules are long, straight cylindrical filaments made from tubulin protein.

Tubulin proteins are heterodimers of alpha and beta tubulin. Each dimer binds GTP at the "nonexchangable site" (N-site), a pocket between the alpha and beta tubulin subunits. Another nucleotide pocket, the "exchangeable site" (E-site) binds GTP, but the nucleotide can be hydrolyded to form GDP.

Dimers self assemble head-to-tail to form protofilaments, and protofilaments aggregate side-by-side to close into a cylindrical microtubule. Most microtubules have 13 protofilaments and are 25 nm wide in outer diameter and 17nm across the inner diameter. In the lab, when we create microtubules outside of cells, they have 9 - 15 protofilaments, and can even shift in protofilament number from one region to the next within the same filament. Most microtubules in cells and in the lab have a “B-lattice” where alpha subunits bind to alpha subunits on the neighboring protofilament. An “A-lattice” where the alpha subunits of one protofilament bind to beta subunits of the neighboring protofilament. In 13-protofilament microtubules, an A-lattice only exists at the seam.

In our lab, we use epi-fluorescence and Total Internal Reflection Fluorescence (TIRF) microscopy to visualize single microtubules and microtubule bundles. We also use Transmission Electron Microscopy (TEM) on negatively stained microtubules to see them at 200,000x normal size (see figure below).

Microtubules are found in all eukaryote cells (cells with a nucleus) and are used for structural support, movement, and active transport conduits. They are the support structures that give the cell shape. This is especially important in long, extended structures, such as the axon and dendrites of nerve cells or in the cilia and flagella of motile cells. See the microtubule mechanics section for more information about the microtubule as a support structure. Microtubules also act as the highway system for long-distance transport within cells. See the microtubule motor section for more information about microtubules as tracks for intracellular transport and intracellular organization.

Microtubules are essential structures for development and proper cellular function. The are used as the main structural element of the mitotic spindle, the machinery used to separate duplicated genetic material (DNA) during cell division. Microtubules can dynamically rearrange from a quiescent interphase cell to a mitotic cell through an inherent ability to grow and shrink, called dynamic instability. For more information on microtubule dynamics, see the microtubule dynamics section. When microtubule organization or dynamics are disrupted, cell division can be affected. This can lead to cancer, and microtubules are a major drug target for chemotherapeutic drugs such as Paclitaxel (Taxol). Some of our early work (2003 - 2004) focused on the activity of Taxol binding to microtubules (see Publications page).