Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.
Bottom Line: In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%).Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK.Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.
Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.Show MeSH
Mentions: The various JIP1b mutants used in this study. and their ability to bind to different regions of KLC1 are summarized in Figure 4A. In addition to the known interaction between JIP1b C11 and TPR motifs of KLC1, two novel interactions were found: binding of the 370–402 and 465–483 regions of JIP1b to the N-terminal region of KLC1, which forms a coiled-coil structure. Furthermore, the 465–483 region of JIP1b plays an important role in regulating the association between JIP1b C11 and TPR motifs of KLC1, or possibly in preserving the physiological conformation of JIP1b, to interact with KLC1. A schematic of the interaction between JIP1b and KLC and its regulation is shown in Figure 4B.
Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.