"Relating single motor function to ensemble transport in cells" by Jing Xu
March 7, 2011 - 10:00am
Cells are highly ordered and organized. Much of the cell’s order relies on the active transport of material by molecular motors. Disruption in intracellular transport can be detrimental to cells, and is a common early theme in neurodegeneration. While molecular motors have been studied in isolated, cell-free system, how they act in groups in cells, and how their group functions are regulated or disrupted, are not yet understood. To address these questions in a concrete, experimentally tractable system, we studied the effects of a neurodegenerative mutation (“Legs at Odd Angles”, or Loa) on the major molecular motor, dynein. Combining single molecule, live cell imaging, and nanometer-level particle tracking techniques, we find that the Loa mutation significantly inhibits dynein travel distance, both at the single molecule level, and as ensemble in the cellular environment of neurons. Our theoretical modeling (constrained by the measured single dynein run lengths) successfully predicted the measured travel defect in mutant neurons. These results validate our current model of multiple-motor based transport, and provide the first direct evidence for a link between single motor run length and disease.