Figure 1.

Phosphorylation of htt regulates BDNF transport directionality. (A) Anterograde and retrograde BDNF vesicular velocities are stimulated by htt in cortical neurites and are inhibited by siRNA targeting htt, p150^Glued, KHC or DHC. The reduction of protein levels by siRNA is shown by immunoblotting. (B) Expression of htt-S421A stimulates retrograde transport, whereas htt-S421D stimulates anterograde transport as shown by kymographs. (C) Mean velocity, (D) scatter plots of translocation velocities as a function of the distance travelled between two pauses are shown. (E) IGF-1 promotes anterograde transport of BDNF vesicles in the scramble RNA condition. This effect is lost in the absence of htt (siRNA-htt). Control: corresponding empty vector (^*P<0.05, ^**P<0.01, ^***P<0.001; see Supplementary data for detailed statistical analyses and number of measures).