Project Summary
Tubulin plays fundamental roles in axon formation, maintenance, and dysfunction. Despite this, how tubulin is
delivered to axons remains highly controversial, and how tubulin is removed from axons is entirely unknown.
This is due to technical challenges in visualizing tubulin movement, that stem from the fact that tubulin is highly
abundant in immobile polymers and that when movement occurs, it is extremely slow. We recently overcame
similar obstacles to the visualization of spectrin delivery to axons. Here we propose to modify, adapt and
validate our methodology in order to generate a new probe for visualizing the axonal delivery and removal of
endogenous tubulin, in vivo, with single-axon resolution. Successful completion of this project will reveal how
tubulin is delivered and removed from axons, and how delivery and removal are balanced to generate a steady
state cytoskeletal mass under different physiological conditions. This knowledge and tools will move the field
forward by opening the way for more mechanistic and disease-focused studies. Furthermore, the approach
could be adapted to visualize the axonal delivery and removal of other slow axonal transport cargo.