Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
Authors
Chiba, KyokoAraseki, 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
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2014-11-05Keywords
Adaptor Proteins, Signal TransducingAmyloid beta-Protein Precursor
Animals
Axonal Transport
COS Cells
Cercopithecus aethiops
Cerebral Cortex
Gene Expression Regulation
Hippocampus
Kinesin
MAP Kinase Kinase 4
Mice
Microscopy, Fluorescence
Microtubule-Associated Proteins
Neurons
Phosphorylation
Plasmids
Primary Cell Culture
Protein Interaction Domains and Motifs
Protein Transport
Signal Transduction
Transfection
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
Metadata
Show full item recordAbstract
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 ( approximately 2.7 mum/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity ( approximately 1.83 mum/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.Source
Mol Biol Cell. 2014 Nov 5;25(22):3569-80. doi: 10.1091/mbc.E14-06-1111. Epub 2014 Aug 27. Link to article on publisher's siteDOI
10.1091/mbc.E14-06-1111Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28281PubMed ID
25165140Related Resources
Link to Article in PubMedRights
© 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).
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http://creativecommons.org/licenses/by-nc-sa/3.0/ae974a485f413a2113503eed53cd6c53
10.1091/mbc.E14-06-1111
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Except where otherwise noted, this item's license is described as <p>© 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).</p>
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