Figure 7.

Phosphorylation of htt at S421 increases anterograde flux and BDNF release. (A) Phosphorylation of htt at S421 increases anterograde flux as quantified by the ratio of the total anterograde travelled distance over the total retrograde travelled distance by BDNF-containing vesicles. (B, C) BDNF release is increased in cortical neurons after IGF-1 treatment or after transfection with the htt-S421D construct. (D) Proposed model of the directionality switch induced by phosphorylation of htt. When htt is not phosphorylated, the kinesin-1 interaction with motor complex is weak, kinesin-1 is detached from MTs and vesicles leading to retrograde transport. When htt is phosphorylated, the kinesin-1 association with motor complex is increased and kinesin-1 is recruited to vesicles, therefore inducing a switch to anterograde transport (^*P<0.05, ^**P<0.01, ^***P<0.001; see Supplementary data for detailed statistical analyses and number of measures).