Figure 6.

Huntingtin is an essential regulator of axonal transport. (A) Anterograde and retrograde transports are inhibited by siRNA targeting kinesin-1 (KHC) compared with the scramble situation. Expressing htt-S421A and htt-S421D in the presence of siRNA-KHC has no stimulatory effects on retrograde or anterograde transport. (B) htt stimulates anterograde and retrograde transport of TI-VAMP-GFP vesicles in cortical neurons (left graph). Absence of phosphorylation at S421 (htt-S421A) favours retrograde transport, and constitutive phosphorylation (htt-S421D) specifically increases anterograde transport (right graph). (C) APP anterograde movement depends on htt and its phosphorylation at S421. The velocity of APP-containing vesicles is reduced in cells with low htt levels (siRNA-htt) compared with a scramble situation. Expressing htt-S421D significantly increases the anterograde velocity of APP-containing organelles compared with htt-S421A (^*P<0.05, ^**P<0.01, ^***P<0.001; see Supplementary data for detailed statistical analyses and number of measures).