Figure 7.

Simulation of vesicle diffusion and microtubule capture in the distal axon. (A) STED image Tyr-microtubules in the neuronal growth cone with the cell border outlined in white (left) and a schematicgrowth cone (right). (B) Median (with bootstrapped 95% CI of the median) for the effective time to microtubule capture in computer simulations with CLIP-E or CLIP-A, and either Tyr or Detyr binding probabilities (D = 0.006um²/sec). (C) Median time to microtubule capture using Tyr binding probabilities and a range of diffusion coefficients (also see Figure S7). (d) Simulated retrograde flux for four different traced neuronal growth cones used in the simulation. In some neurons, CLIP-A decoration increases the simulated retrograde flux. (e) Working model for the regulation of transport initiation in neurons. A gradient of tyrosinated α-tubulin is enriched in the distal axon provides spatial regulation and promotes efficient binding in a region where many cargos originate. CLIP-170 is highly phosphorylated and not microtubule associated in the growth cone at baseline. Transient or local dephosphorylation may provide temporal regulation and is required for efficient transport initiation in neurons.