| Title: | Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport |
| Authors: | Chiba, Kyoko Browse this author |
| Araseki, Masahiko Browse this author |
| Nozawa, Keisuke Browse this author |
| Furukori, Keiko Browse this author |
| Araki, Yoichi Browse this author |
| Matsushima, Takahide Browse this author |
| Nakaya, Tadashi Browse this author →KAKEN DB |
| Hata, Saori Browse this author →KAKEN DB |
| Saito, Yuhki Browse this author →KAKEN DB |
| Uchida, Seiichi Browse this author →KAKEN DB |
| Okada, Yasushi Browse this author →KAKEN DB |
| Nairn, Angus C. Browse this author |
| Davis, Roger J. Browse this author |
| Yamamoto, Tohru Browse this author →KAKEN DB |
| Kinjo, Masataka Browse this author →KAKEN DB |
| Taru, Hidenori Browse this author →KAKEN DB |
| Suzuki, Toshiharu Browse this author →KAKEN DB |
| Issue Date: | 5-Nov-2014 |
| Publisher: | American Society for Cell Biology |
| Journal Title: | Molecular biology of the cell |
| Volume: | 25 |
| Issue: | 22 |
| Start Page: | 3569 |
| End Page: | 3580 |
| Publisher DOI: | 10.1091/mbc.E14-06-1111 |
| PMID: | 25165140 |
| Abstract: | Alzheimer's beta-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (similar to 2.7 mu m/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (similar to 1.83 mu m/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11-amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/57645 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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