I propose to investigate microtubule dynamics in living growth cones and determine how filamentous-actin (F-actin) and microtubules (MTs) influence each others distribution and dynamics. Recent advances in electronic imaging technology now make it possible to directly ascertain and measure these cytoskeletal polymer dynamics in living cells. The significance of investigating cytoskeletal protein dynamics lies in the fact that their rearrangement represents a final effector mechanism common to essentially all forms motility. Thus, determining the parameters of polymer dynamics in the grnwth cone will provide a basis for asking higher order questions such as how regulatory pathways couple extracellular signals to cytoskeletal remodeling. Specifically, I will: 1) Determine the biophysical parameters of MT dynamics in neuronal growth cones. 2) Determine the effect of F-actin disruption on MT movements. 3) Investigate the interrelationships between MT and F-actin dynamics by dual visualization of MTs and F-actin. 4) Determine the mechanism of directed microtubule advance (sliding versus polymerization) during growth cone turning/target interactions.
| Zhang, Xiao-Feng; Schaefer, Andrew W; Burnette, Dylan T et al. (2003) Rho-dependent contractile responses in the neuronal growth cone are independent of classical peripheral retrograde actin flow. Neuron 40:931-44 |
| Schaefer, Andrew W; Kabir, Nurul; Forscher, Paul (2002) Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones. J Cell Biol 158:139-52 |
| Kabir, N; Schaefer, A W; Nakhost, A et al. (2001) Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes. J Cell Biol 152:1033-44 |
