Effect of G4C2 Repeat Expansions on the Motion of1 Lysosomes Inside Neurites.

Data concerning the above-mentioned paper.

Abstract

The G4C2 hexanucleotide repeat expansion (HRE) in the c9orf72 locus is a mutation associated with amyotrophic lateral sclerosis,  and recent evidence suggests a link with disrupted axonal trafficking in neurons.         Here, using a neuron-like cell line without, or transfected with, G4C2 repeats, we characterize the motion of lysosomes inside neurites which were either aligned or oriented randomly on the substrate, implementing time-resolved (local) mean squared displacement (l)MSD analysis and differentiation among sub-diffusive, diffusive, and super-diffusive trajectory parts.        Our results suggest that in the presence of the G4C2 repeats, lysosome motility is hampered, exhibiting overall decreased MSD and speed, more prominently inside aligned neurites.     Moreover, a more prominent effect in the super-diffusive drift velocity and diffusive motion diffusion coefficient was evident when the motion occurred inside aligned neurites.     Trajectories which included super-diffusive motion, exhibited a varied ratio of anterograde/retrograde/neutral for both neurite geometries in the presence of G4C2 repeats but a similar instantaneous velocity decrease for both directions in each neurite geometry.    Our findings support the hypothesis that impaired axonal trafficking emerges in the presence of the G4C2 HRE, and demonstrate that this effect is more prominent when the neurites are aligned.