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
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Mentions: Our observations indicate that 1) the interaction between the TPR motifs of KLC1 and the C11 region, including Tyr-705 of JIP1b, is essential for the enhanced fast anterograde transport of APP cargo; 2) a novel element within amino acids 370–402 of JIP1b is required for preservation and/or stabilization of the higher frequency of APP anterograde transport through interaction with the N-terminal region of KLC1; 3) another novel element, amino acids 465–483 of JIP1b, regulates the interaction of the KLC1 TPR domain with the JIP1b C11 domain through an association with the N-terminal region of KLC1; 4) this interaction may also contribute to APP cargo stabilization and/or activation of anterograde transport; and 5) phosphorylation of APP at Thr-668 does not contribute to the increased efficiency of APP cargo transport. The functional interactions among APP, JIP1b, and KLC of kinesin-1 are illustrated in Figure 6.
Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.