Microtubule Motor Proteins
Microtubules form the tracks for motor proteins that are required for intracellular transport in cells. Motors proteins are nanoscale enzymes that literally “walk” along microtubules carrying cellular cargos on their heads to bring molecules, macromolecular complexes, and organelles around the cell. For a review, please see: J.L. Ross, M.Y. Ali, D.M. Warshaw, “Cargo transport: Molecule motors navigate a complex cytoskeleton,” Current Opinion in Cell Biology, 20, 41-47 (2008). webRoss-COCB-2008.pdf. We are currently working on understanding the transport of self-assembled cargos that mimic transiently complexes proteins of slow axonal transport.
Microtubules with motor proteins are responsible for the spatial temporal organization of vesicular organelles and compartments within the cell. In no system is this more important than the long axons of nerve cells that can be up to one meter in length to connect your spine to your pinky toe. Without intracellular transport to bring new materials to the tip of the cell, the growth cone, and remove degraded materials out of that area, the axons of nerve cells could degrade. This does occur during diseases of the neuromuscular system, such as Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease), which is the disease that affects physicist Stephen Hawking.
As a postdoctoral researcher, I used single molecule imaging to visualize single dynein and kinesin motors as they walked along microtubules J.L. Ross, K. Wallace, H. Shuman, Y.E. Goldman, E.L.F. Holzbaur, “Single Dynein-Dynactin Complexes Exhibit Bi-Directional Motion in vitro,” Nature Cell Biology, 8, 562-570 (2006). web Ross-NCB-2006.pdf. We also tested their abilities to navigate through microtubule intersections J.L. Ross, H. Shuman, E.L.F. Holzbaur, Y.E.Goldman, “Kinesin and dynein-dynactin at intersecting microtubules: Motor density affects dynein function,” Biophysics Journal, 94, 3115-3125 (2008). web Ross-BPJ-2008.pdf and around obstacles R. Dixit, J.L. Ross, Y.E.Goldman, E.L.F.Holzbaur, “Differential regulation of dynein and kinesin motor proteins by tau,” Science, 319, 1086-1089 (2008). web Dixit-Science-2008.pdf.
Motors can also rearrange microtubules themselves in cells. We have begun to explore these motor-based patterns using gliding microtubules at high densities: L. Liu, E. Tuzel, J.L. Ross, “Loop formation in microtubules during gliding at high density,” Journal of Physics: Condensed Matter Special Issue: Cooperative Dynamics in Cells, 23, 374104 (2011) web Liu-JoPCM-2011.pdf (*Chosen as a top article for 2011!) We are continuing this work by adding crosslinking associated proteins to increase the complexity of these systems.