Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK.

The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.

The diffusive interaction of microtubule binding proteins.

Microtubule-based motility is often thought of as specifically referring to the directed stepping of microtubule-based motors such as kinesin or dynein. However, microtubule lattice diffusion (also known as diffusional motility) provides a second mode of transport that is shared by a much broader class of microtubule binding proteins. Microtubule lattice diffusion offers distinct advantages as a transport mechanism including speed, bidirectional microtubule end targeting, and no requirement for direct chemical energy (i.e. ATP). It remains to be seen whether a universal binding mechanism for this interaction will be identified but electrostatic interactions appear to play a significant role. In the meantime, the well-studied subject of DNA binding proteins that diffuse along the DNA backbone provides an insightful analog for understanding the nature of microtubule-based diffusional motility.