Figure 16–54 Sequestration of tubulin by stathmin. Structural studies with electron microscopy and crystallography suggest that the elongated stathmin protein binds along the side of two tubulin heterodimers. (Adapted from M.O. Steinmetz et al., EMBO J. 19:572–580, 2000. With permission from John Wiley and Sons.) “sword,” accomplishes this demanding task (Figure 16–55). Katanin is made up of two subunits: a smaller subunit that hydrolyzes ATP and performs the actual severing, and a larger one that directs katanin to the centrosome. Katanin releases microtubules from their attachment to a microtubule-organizing center and is thought to contribute to the rapid microtubule depolymerization observed at the poles of spindles during mitosis. It may also be involved in microtubule release and depolymerization in proliferating cells in interphase and in postmitotic cells such as neurons.
Two Types of Motor Proteins Move Along Microtubules
Like actin filaments, microtubules also use motor proteins to transport cargo and perform a variety of other functions within the cell. There are two major classes of microtubule-based motors, kinesins and dyneins. Kinesin-1, also called “conventional kinesin,” was first purified from squid neurons, where it carries membrane-enclosed organelles away from the cell body toward the axon terminal by walking toward the plus end of microtubules. Kinesin-1 is similar to myosin II in having two heavy chains per active motor; these form two globular head motor domains that are held together by an elongated coiled-coil tail that is responsible for heavy-chain dimerization. One kinesin-1 light chain associates with each heavy chain through its tail domain and mediates cargo binding. Like myosin, kinesin is a member of a large protein superfamily, for which the motor domain is the common element (Figure 16–56). The yeast Saccharomyces cerevisiae has six distinct kinesins. The nematode C. elegans has 20 kinesins, and humans have 45.
There are at least fourteen distinct families in the kinesin superfamily. Most of them have the motor domain at the N-terminus of the heavy chain and walk toward the plus end of the microtubule. One family has the motor domain at the C-terminus and walks in the opposite direction, toward the minus end of the microtubule, while kinesin-13 has a central motor domain and does not walk at all, but uses the energy of ATP hydrolysis to depolymerize microtubule ends, as described above (see Figure 16–52). Some kinesin heavy chains are homodimers, and others are heterodimers. Most kinesins have a binding site in the tail for another microtubule; alternatively, they may link the motor to a membrane-enclosed organelle via a light chain or an adaptor protein. Many of the kinesin superfamily members have specific roles in mitotic spindle formation and in chromosome segregation during cell division.
In kinesin-1, instead of the rocking of a lever arm, small movements at the nucleotide-binding site regulate the docking and undocking of the motor head domain to a long linker region. This acts to throw the second head forward along
Figure 16–55 Microtubule severing by katanin. Taxol stabilized, rhodaminelabeled microtubules were adsorbed on the surface of a glass slide, and purified katanin was added along with ATP. (A) There are a few breaks in the microtubules 30 seconds after the addition of katanin. (B) The same field 3 minutes after the addition of katanin. The filaments have been severed in many places, leaving a series of small fragments at the previous locations of the long microtubules. (From J.J. Hartman et al.,  Cell 93:277–287, 1998. With permission from Elsevier.)