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Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport

Alzheimer's β-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-...

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Autores principales: Chiba, Kyoko, Araseki, Masahiko, Nozawa, Keisuke, Furukori, Keiko, Araki, Yoichi, Matsushima, Takahide, Nakaya, Tadashi, Hata, Saori, Saito, Yuhki, Uchida, Seiichi, Okada, Yasushi, Nairn, Angus C., Davis, Roger J., Yamamoto, Tohru, Kinjo, Masataka, Taru, Hidenori, Suzuki, Toshiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230617/
https://www.ncbi.nlm.nih.gov/pubmed/25165140
http://dx.doi.org/10.1091/mbc.E14-06-1111
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author Chiba, Kyoko
Araseki, Masahiko
Nozawa, Keisuke
Furukori, Keiko
Araki, Yoichi
Matsushima, Takahide
Nakaya, Tadashi
Hata, Saori
Saito, Yuhki
Uchida, Seiichi
Okada, Yasushi
Nairn, Angus C.
Davis, Roger J.
Yamamoto, Tohru
Kinjo, Masataka
Taru, Hidenori
Suzuki, Toshiharu
author_facet Chiba, Kyoko
Araseki, Masahiko
Nozawa, Keisuke
Furukori, Keiko
Araki, Yoichi
Matsushima, Takahide
Nakaya, Tadashi
Hata, Saori
Saito, Yuhki
Uchida, Seiichi
Okada, Yasushi
Nairn, Angus C.
Davis, Roger J.
Yamamoto, Tohru
Kinjo, Masataka
Taru, Hidenori
Suzuki, Toshiharu
author_sort Chiba, Kyoko
collection PubMed
description Alzheimer's β-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 (∼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%). 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.
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spelling pubmed-42306172015-01-20 Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport Chiba, Kyoko Araseki, Masahiko Nozawa, Keisuke Furukori, Keiko Araki, Yoichi Matsushima, Takahide Nakaya, Tadashi Hata, Saori Saito, Yuhki Uchida, Seiichi Okada, Yasushi Nairn, Angus C. Davis, Roger J. Yamamoto, Tohru Kinjo, Masataka Taru, Hidenori Suzuki, Toshiharu Mol Biol Cell Articles Alzheimer's β-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 (∼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%). 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. The American Society for Cell Biology 2014-11-05 /pmc/articles/PMC4230617/ /pubmed/25165140 http://dx.doi.org/10.1091/mbc.E14-06-1111 Text en © 2014 Chiba, Araseki, Nozawa, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Chiba, Kyoko
Araseki, Masahiko
Nozawa, Keisuke
Furukori, Keiko
Araki, Yoichi
Matsushima, Takahide
Nakaya, Tadashi
Hata, Saori
Saito, Yuhki
Uchida, Seiichi
Okada, Yasushi
Nairn, Angus C.
Davis, Roger J.
Yamamoto, Tohru
Kinjo, Masataka
Taru, Hidenori
Suzuki, Toshiharu
Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title_full Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title_fullStr Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title_full_unstemmed Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title_short Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
title_sort quantitative analysis of app axonal transport in neurons: role of jip1 in enhanced app anterograde transport
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230617/
https://www.ncbi.nlm.nih.gov/pubmed/25165140
http://dx.doi.org/10.1091/mbc.E14-06-1111
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